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TRIM29 is involved in DNA double‐strand break repair but the specific roles of TRIM29 in DNA repair are not clearly understood. We proposed that TRIM29 regulates the choice of DNA DSB repair pathway by facilitating 53BP1 accumulation to promote NHEJ, possibly through RNF8 or TIP60., Tripartite motif‐containing protein 29 (TRIM29) is involved in DNA double‐strand break (DSB) repair. However, the specific roles of TRIM29 in DNA repair are not clearly understood. To investigate the involvement of TRIM29 in DNA DSB repair, we disrupted TRIM29 in DT40 cells by gene targeting with homologous recombination (HR). The roles of TRIM29 were investigated by clonogenic survival assays and immunofluorescence analyses. TRIM29 triallelic knockout (TRIM29 −/−/−/+) cells were sensitive to etoposide, but resistant to camptothecin. Foci formation assays to assess DNA repair activities showed that the dissociation of etoposide‐induced phosphorylated H2A histone family member X (ɣ‐H2AX) foci was retained in TRIM29 −/−/−/+ cells, and the formation of etoposide‐induced tumor suppressor p53‐binding protein 1 (53BP1) foci in TRIM29 −/−/−/+ cells was slower compared with wild‐type (WT) cells. Interestingly, the kinetics of camptothecin‐induced RAD51 foci formation of TRIM29 −/−/−/+ cells was higher than that of WT cells. These results indicate that TRIM29 is required for efficient recruitment of 53BP1 to facilitate the nonhomologous end‐joining (NHEJ) pathway and thereby suppress the HR pathway in response to DNA DSBs. TRIM29 regulates the choice of DNA DSB repair pathway by facilitating 53BP1 accumulation to promote NHEJ and may have potential for development into a therapeutic target to sensitize refractory cancers or as biomarker of personalized therapies.

Aim This cross-sectional study investigated the effect of the vitamin D receptor (VDR) FokI polymorphism and its interactions with smoking/drinking on the proportions of periodontal pathogens and periodontitis severity. Materials and methods FokI genotyping and bacterial quantification were performed using real-time polymerase chain reaction. Periodontitis severity was determined using mean clinical attachment level (CAL). Regression analyses examined the associations between the FokI polymorphism (rs2228570) and bacterial proportions or periodontitis severity. Effect modification by smoking or drinking was assessed. Results The study population comprised 1,460 individuals, aged 39-66 years. After multivariable adjustment, the FokI risk genotypes (CC + CT) were associated with elevated Porphyromonas gingivalis proportions (regression coefficient (β) =0.294 ± 0.139; p = .034) and increased mean CAL (β = 0.130 ± 0.048; p = .007). The effect of the FokI polymorphism on P. gingivalis proportions was greater in smokers (β = 0.897 ± 0.328; p = .006) compared to non-smokers (β = 0.164 ± 0.153; p = .282) and in drinkers (β = 0.668 ± 0.242; p = .006) compared to non-drinkers (β = 0.114 ± 0.169; p = .500). The genotype*smoking interaction for P. gingivalis proportions was significant (p = .043), whereas the genotype*drinking interaction was not (p = .061). Similar results were found for the effect of the genotype*smoking/drinking interaction on mean CAL. Conclusions These findings suggest that the interplay between the host genotype and smoking is important in determining the subgingival microbial composition and periodontitis severity.

Background Curcumin has been claimed to have gastrointestinal benefits including dyspepsia—a common disorder that could be managed in a primary care setting with behavioral and dietary modification as well as over-the-counter medications. This study aimed to compare the efficacy of curcumin versus omeprazole in improving patient-reported outcomes. Methods This randomized controlled trial comprised of three arms of four large (250 mg of curcumin or placebo) and one small (20 mg of omeprazole or placebo) capsules: curcumin only (C), omeprazole only (O), and curcumin+omeprazole (C+O). The large capsules were taken four times daily and the small capsules were taken twice daily for 28 days. Eligible participants with dyspepsia symptoms, assessed by using the Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ), underwent gastroscopy by certified gastroenterologists; those with pathologic dyspepsia including Helicobacter pylori infection were excluded. Functional dyspepsia symptoms were assessed by using the Severity of Dyspepsia Assessment (SODA) scores at baseline, day 28, and day 56. Demographics and clinical characteristics were analyzed by using descriptive statistics. Comparative improvement of SODA scores across the three arms, adjusted for potential confounders, were analyzed by using generalized estimating equations (GEE) regression. Results A total of 207 participants; C (69), O (69), C+O (69), were recruited, of which 151; C (49), O (49), C+O (53) completed the study. The overall mean age was 49.7±11.9 years and 73.4% were female. Demographics, clinical characteristics, baseline SODA, and SF-LDQ scores were comparable across the three groups. The SODA pain intensity reduction (C: -6.22 and -9.59; O: -6.98 and -10.62; C+O: -5.41 and -8.23) and SODA non-pain symptoms improvement (C: -2.45 and -4.77; O: -2.55 and -4.59; C+O: -2.41 and -4.65) were not significantly different across the three groups at day 28 (p=0.491 and 0.964) and 56 (p=0.259 and 0.462), respectively. No serious adverse events were observed. Conclusions Curcumin and omeprazole have comparable efficacy for functional dyspepsia with no obvious synergistic effect.

Introduction Pheochromocytomas and paragangliomas (PPGLs) are highly heritable tumours, with up to 40% of cases carrying germline variants. Current guidelines recommend genetic testing for all patients with PPGLs. Next-generation sequencing (NGS) enables accurate, fast, and inexpensive genetic testing. This study aimed to compare the costs related to PPGL genetic testing between the sequential testing using the decisional algorithm proposed in the 2014 Endocrine Society guidelines and targeted NGS gene panels. Methods Patients with proven PPGLs were enrolled. A gene list covering 17 susceptibility genes related to hereditary PPGLs was developed for targeted sequencing. Validation was carried out by Sanger sequencing. We simulated the diagnostic workflow to examine the anticipated costs based on each strategy for genetic testing. Results Twenty-nine patients were included, among whom a germline variant was identified in 34.5%. A total of 22.7% with apparently sporadic PPGL carried a variant. Five genes were involved (RET, n = 3; SDHB, n = 3; SDHD, n = 2; EGLN1, n = 1; and NF1, n = 1). According to the diagnostic workflow, the average cost of the targeted NGS (534.7 US dollars per patient) is lower than that of the sequential testing (734.5 US dollars per patient). The targeted NGS can also reduce the number of hospital visits from 4.1 to 1 per person. The cost can be further reduced to 496.24 US dollars per person (32% reduction) if we apply a new syndromic-driven diagnostic algorithm to establish priorities for specific genetic testing for syndromic and selected cases, and targeted NGS for non-syndromic patients. Conclusions Targeted NGS can reduce both the cost of PPGL genetic testing and the number of hospital visits, compared with the conventional approach. Our proposed algorithm is the preferred approach due to its significant reduction of the cost of genetic testing.Key messagePheochromocytomas and paragangliomas are highly heritable neoplasms.The targeted next-generation sequencing (NGS) gene panels have proven to be fast, accurate, and inexpensive for the genetic analysis.According to this cost analysis, it is economically reasonable to use targeted NGS gene panels for genetic screening.

Spinal muscular atrophy (SMA) is one of the leading causes of death in infants and young children from heritable diseases. Patients diagnosed with SMA develop symmetrical progressive muscle weakness and atrophy from degeneration of alpha motor neurons. Approximately 95% of patients have a homozygous deletion of survival motor neuron 1 (SMN1) gene in exon 7 and inherited in autosomal recessive pattern. Considering the high prevalence of SMA carrier in many population, it is possible that SMA is one of the most common autosomal recessive disorders in Thailand and Southeast Asia. In this study, we analyzed DNA from peripheral blood of 505 healthy Thai adults using quantitative PCR-based for SMN1 gene exon 7 copy number analysis. Individual samples with heterozygous deletion of SMN1 gene were confirmed with MLPA. The result identified 9 samples (1.78%) with heterozygous deletion and 39 samples as more than 2 copies of SMN1. No homozygous deletion was detected in the samples. In conclusion, we established carrier frequency of SMA in selected Thai population at 1.8% from 505 participants. The prevalence coincides with prevalence in East Asia and Caucasian population. The result could be implemented for SMA carrier screening in couples at risk in the region.

Polymorphisms of the vitamin D receptor (VDR) gene have been implicated in susceptibility to infections and bone-related diseases. However, their relationship with periodontal disease remains unclear. This cross-sectional study investigates whether susceptibility to chronic periodontitis (CP) in a Thai population is associated with VDR polymorphisms.Genomic DNA was obtained from 1,460 participants, aged 39 to 66 years. Genotyping of VDR polymorphisms (FokI, BsmI, ApaI, and TaqI) was performed using real-time polymerase chain reaction. Participants were categorized into three groups: 1) no/mild; 2) moderate; and 3) severe CP. Multinomial logistic regression was used to determine degree of association between VDR polymorphisms and periodontal status adjusted for known confounders.The CC+CT genotypes of FokI polymorphism were associated with severe CP with an odds ratio (OR) of 1.9 (95% confidence interval [CI]: 1.3 to 2.8). Compared with genotype-negative (TT) non-smokers, positivity for the risk genotypes (CC+CT) alone and current smoking alone were associated with severe CP with ORs of 1.8 (95% CI: 1.1 to 3.2) and 2.5 (95% CI: 1.0 to 6.2), respectively. The combination of being genotype positive and smoking further increased the OR to 9.6 (95% CI: 4.5 to 20.4). This combined effect was 3.7 times (95% CI: 1.2 to 11.1) greater than expected from the sum of their individual effects, indicating a synergistic interaction. No significant association was observed between other polymorphisms and CP.FokI CC+CT genotypes were associated with increased susceptibility to severe CP, which was aggravated further when combined with smoking.

Mutations in the VHL, RET, SDHB , and SDHD genes are responsible for von Hippel-Lindau (VHL) disease, multiple endocrine neoplasia type 2 (MEN2), and familial paraganglioma, respectively. However, genotype-phenotype correlation data are lacking in Southeast Asia. A retrospective medical chart review was performed on patients referred to the genetics service. We found 35 patients diagnosed with clinical syndromes (16 VHL, 9 MEN2, 9 paragangliomas, and 1 neurofibromatosis type 1). In patients with VHL, 5 known VHL mutations were identified: p.Trp88X, p.Ile151Thr, p.Arg161X, p.Arg167Gln, and p.Leu178Arg. The most frequent RET mutations in patients with MEN2A occurred at codon 634 on exon 11: p.Cys634Tyr, p.Cys634Trp, and p.Cys634Arg. A patient with MEN2B had p.Met918Thr RET mutation. Approximately, 90% of patients with MEN2 had medullary thyroid carcinoma. Pheochromocytoma was found in 55.6% of patients with MEN2, and 60% of them had bilateral lesions. One patient with malignant thoracic paraganglioma had p.Arg46X mutation of SDHB . This study provides mutation phenotypes that offer a useful tool for clinicians and patients to stratify disease risks and tailor screening programs.

The Professional Society of Genetic Counselors in Asia (PSGCA) was recently established as a special interest group of the Asia Pacific Society of Human Genetics. Fostering partnerships across the globe, the PSGCA’s vision is to be the lead organization that advances and mainstreams the genetic counseling profession in Asia and ensures individuals have access to genetic counseling services. Its mission is to promote quality genetic counseling services in the region by enhancing practice and curricular standards, research and continuing education. The PSGCA was formally launched during the Genetic Counseling Pre-Conference Workshop held at the 11th Asia-Pacific Conference on Human Genetics in Hanoi, Viet Nam, September 16, 2015. The pre-conference workshop provided an opportunity for medical geneticists and genetic counselors from across 10 Asia Pacific countries to learn about the varied genetic counseling practices and strategies for genetic counseling training. This paper provides an overview of the current status and challenges in these countries, and proposed course of unified actions for the future of the genetic counseling profession.

Paraoxonase (PON1, EC 3.1.8.1) is tightly linked to high-density lipoprotein (HDL) and shows significant correlation with apo AI concentrations. It plays an important role in functions such as protection against vascular disease (e.g., atherosclerosis) through its inhibition of low-density lipoprotein (LDL) oxidation and detoxification of organophosphorus compounds by hydrolyzing the bioactive oxons (Mackness et al. 1991). The activity of PON1 is modulated by genetic and environmental factors. Two coding region polymorphisms of the PON1 gene result in amino acid substitutions at position 192 (PON1 Q192R, glutamine to arginine) and at position 55 (PON1 L55 M, leucine to methionine). PON1 Q192R has been reported to account for 73–76% of the variation in hydrolysis activity of paraoxon (paraoxonase activity) and 12–25% of the variation in activity for the hydrolysis of diazoxon (diazonase activity) in vitro (Jarvik et al. 2000). The L55 M polymorphism also contributes to PON1 protein stability and activity (Leviev et al. 2001). PON1 polymorphisms have been studied in many populations of the world; the frequency of the low-activity

Leber hereditary optic neuropathy (LHON) is the most common mitochondrially inherited disease causing blindness, preferentially in young adult males. Most of the patients carry the G11778A mitochondrial DNA (mtDNA) mutation. However, the marked incomplete penetrance and the gender bias indicate some additional genetic and/or environmental factors to disease expression. Herein, we first conducted a genome-wide linkage scan with 400 microsatellite markers in 9 large Thai LHON G11778A pedigrees. Using an affecteds-only nonparametric linkage analysis, 4 regions on chromosomes 3, 12, 13 and 18 showed Zlr scores greater than 2 (P0.025), which is consistently significant across several linkage statistics. The most suggestive marker D3S1565 (Zlr2 in 10 of 16 allele sharing models tested) was then expanded to include the region 3q26.2-3q28 covering SLC7A14 (3q26.2), MFN1 (3q26.32), MRPL47 (3q26.33), MCCC1 (3q27.1), PARL (3q27.1) and OPA1 (3q28-q29). All of these candidate genes were selected from the Maestro database and had known to be localized in mitochondria. Sixty tag SNPs were genotyped in 86 cases, 211 of their relatives and 32 unrelated Thai controls, by multiplex-PCR-based Invader assay. Analyses using a powerful association testing tool that adjusts for relatedness (the M(QLS) statistic) showed the most evidence of association between two SNPs, rs3749446 and rs1402000 (located in PARL presenilins-associated rhomboid-like) and LHON expression (both P = 8.8 x 10(-5)). The mitochondrial PARL protease has been recently known to play a role with a dynamin-related OPA1 protein in preventing apoptotic events by slowing down the release of cytochrome c out of mitochondrial cristae junctions. Moreover, PARL is required to activate the intramembranous proteolyses resulting in the degradation of an accumulated pro-apoptotic protein in the outer mitochondrial membrane. Under these circumstances, variants of PARL are suggested to influence cell death by apoptosis which has long been believed to intrigue the neurodegeneration of LHON.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of disorders with almost 30 subtypes. The prevalence and relative frequency of each subtype vary among different populations. In this article, we report the relative frequency of six SCA subtypes in the Thai population and attempt to explain the observed pattern when compared with other populations in this region. We searched for SCA type 1, SCA2, SCA3, SCA6, SCA7 and dentatorubral-pallidoluysian atrophy mutations using GeneScan analysis in 340 patients from 182 families, in which at least one person had a clinical diagnosis of SCA. We analyzed the relative frequencies of SCA subtypes on a family basis, and compared these with the data in the Chinese and Indian populations. SCA3 was found in 19.2% of the patients (Agresti-Coull 95% confidence interval: 14.1-25.6%), SCA1 in 11.5% (7.6-17.1%) and SCA2 in 10.4% (6.7-15.8%). SCA6 was found in three families, with a relative frequency of 1.6% (0.3-5.0%). Compared with the related populations, the Thai SCA3 frequency was less than that of the Chinese, whereas it was higher than that in most of the Indian studies. The reverse is true for the SCA1/SCA2 frequency. A similar study in Singapore, where there was a clear history of population admixture, also showed the frequencies between those of the Chinese and the Indian populations. Although SCA3 was the most common identifiable SCA subtype in Thailand, SCA1 and SCA2 were also relatively common. Our results also supported some degree of admixture with the Indians in the Thai population and justify further study in the area.

Tuberculosis, a potentially fatal infectious disease, affects millions of individuals annually worldwide. Human protective immunity that contains tuberculosis after infection has not been clearly defined. To gain insight into host genetic factors, nonparametric linkage analysis was performed using high-throughput microarray-based single nucleotide polymorphism (SNP) genotyping platform, a GeneChip array comprised 59 860 bi-allelic markers, in 93 Thai families with multiple siblings, 195 individuals affected with tuberculosis. Genotyping revealed a region on chromosome 5q showing suggestive evidence of linkage with tuberculosis (Z(lr) statistics=3.01, logarithm of odds (LOD) score=2.29, empirical P-value=0.0005), and two candidate regions on chromosomes 17p and 20p by an ordered subset analysis using minimum age at onset of tuberculosis as the covariate (maximum LOD score=2.57 and 3.33, permutation P-value=0.0187 and 0.0183, respectively). These results imply a new evidence of genetic risk factors for tuberculosis in the Asian population. The significance of these ordered subset results supports a clinicopathological concept that immunological impairment in the disease differs between young and old tuberculosis patients. The linkage information from a specific ethnicity may provide unique candidate regions for the identification of the susceptibility genes and further help elucidate the immunopathogenesis of tuberculosis.

Background: Duchenne muscular dystrophy (DMD), a lethal X-linked disease affecting 1 in 3500 male births, and its more benign variant, Becker muscular dystrophy (BMD), are caused by mutations in the dystrophin gene. Because of its large size, analysing the whole gene is impractical. Methods have been developed to detect the commonest mutations i.e. the deletions of the exons. Although these tests are highly specific, their sensitivity is inherently limited by the prevalence of deletions, which differs among different populations.Methods: We reviewed our database for the detection of Dystrophin gene mutation by means of 31-exon multiplex PCR in Thai males, diagnosed clinically and biochemically with DMD or BMD from July 1994 to November 2006. One index patient was chosen from each family for statistical analysis. The overall sensitivity of the test, the number of fragment deleted, and the deletion frequency of each fragment were calculated, along with their 95% confidence intervals (C.I.).Results: We found deletions in 99 out of the 202 index patients (49%; Bayesian 95% C.I. = 42%–56%). 51% of these had deletion in only one of the 31 exons tested, while the patient with the most extensive deletions had 14 exons deleted. The mean number of deleted exons were 2.84 (BCabootstrap 95% C.I. = 2.37–3.48), or 5.02 (3.81–6.85) if all the untested exons adjacent to the confirmed deleted exons were assumed to be deleted. The region spanning exons 44-52 was the most frequently deleted. These were similar to those reported in the Japanese.Conclusion: The multiplex PCR detected deletions only in about half of the Thai patients. The diseases therefore should not be excluded solely on the negative result if DMD/BMD is strongly suspected.

Nevirapine (NVP) is commonly used as a component of first-line antiretroviral therapy in resource-limited countries. We aimed to determine the risk factors for NVP-associated rash among HIV-infected patients who were initiated NVP at low CD4 cell counts in a resource-limited setting. A case-control study was conducted in HIV-infected patients who developed rash after taking NVP (case) and those who did not have rash (control). A total of 357 patients with a mean (SD) age of 36.4 (7.5) years and 52.1% male were included in the study. Mean body weight (SD) was 55.5 (10.5) kg. Of all, 179 (49.0%) patients had a history of AIDS-defining illness and 57 (16.0%) patients had history of drug allergy. Median (IQR) CD4 cell counts at the time of NVP initiation was 95 (31-226) cells/mm(3). There were 115 patients in case group and 242 patients in control group. In case group, 43.0%, 54.4%, and 2.6% of patients developed grade 2, 3, and 4 of rash, respectively. Median time to develop rash was 12 (95%CI, 10.5-13.5) days. By logistic regression, history of drug allergy (OR, 3.41; 95%CI, 1.79-6.52), body weight (OR, 1.22 per each 5 kg decrement; 95%CI, 1.08-1.38), CD4 cells counts (OR, 1.20 per each 50 cells/mm(3) increment; 95%CI, 1.12-1.30), and AIDS-defining illness (OR, 0.42; 95%CI, 0.25-0.70) were significantly associated with rash. In resource-limited settings where patients were initiated NVP at low CD4 cell counts, history of drug allergy, lower body weight, and higher CD4 cell count are the risk factors for NVP-associated rash. Initiation of NVP in patients with these risks needs closed monitoring.

Haemoglobin (Hb) Hope [beta136(H14)Gly-->Asp(GGT-->GAT)] is one of the unstable haemoglobin variants of the beta-globin chain, which is demonstrated in people of various ethnic backgrounds. Here we report a Thai female patient with clinical thalassaemia intermedia since childhood. This patient had experienced neither blood transfusion nor hospitalisation. Hb Bart's-H and a large amount of Hb Hope were identified by high-performance liquid chromatography (HPLC) assay and the diagnosis of homozygous Hb Hope was definitely achieved by direct sequencing of exon 3 of beta-globin gene. Furthermore, we could identify that her brother carried the mutation of homozygous Hb Hope without abnormal alpha globin chain involvement, and another family member had heterozygous Hb Hope in association with -alpha(3.7) mutation, and both of them were clinically silent.

We report on a Thai female patient who presented with hypochromic microcytic anemia, hepatosplenomegaly, and failure to thrive since 3 years of age. Hematological and hemoglobin (Hb) analysis were consistent with a clinical diagnosis of Hb H disease. However, no abnormal Hb fraction had ever been detected. During the 20 years of follow-up, this patient experienced several episodes of hemolytic crisis, which worsened her anemia, necessitating blood transfusion. Recently, we identified Hb Quong Sze (Hb QS), a highly unstable globin gene mutation affecting codon 125 (CTG-->CCG) of alpha(2) globin gene in trans with the commonest alpha(0) thalassemia (-(SEA)) in the patient. This report highlights the clinical significance of Hb QS in Southeast Asians, as previously almost all of the patients described with this variant were of Chinese origin.

Bone marrow transplantation is the only therapeutic option that can potentially eliminate thalassemic disease. Early results indicated that children in Class 3 Lucarelli had a much worse outcome because of high nonrejection mortality and high rejection rate. In the present study, reduced intensity stem cell transplantation (RIT) was performed in eight Class 3 Lucarelli patients conditioned by busulfan, fludarabine, and antilymphpcute globulin. One of the eight patients additionally received thiotepa, and total lymphoid irradiation (TLI), while one only received TLI. All patients received hydroxyurea 20 mg/kg/day daily >/=3 months before RIT. Peripheral blood stem cell (PBSCs) were given to a target number of CD34(+) cells more than 5 x 10(6) cells/kg of recipient weight. Seven patients received T cell nondepleted PBSCs from matched siblings while one patient received purified CD34(+) cells from two HLA antigen mismatched maternal PBSCs. The graft-versus-host disease (GvHD) prophylaxis included cyclosporine or tacrolimus and mycophenolate mofetil. Initially, an engraftment of donor cells was observed in all eight patients, but subsequently only six of eight patients had stable full donor engraftment. There were no deaths or Grade 3-4 acute GvHD in our patients. The present study lends support that the regimens described here produced minimal toxicity and resulted in stable full donor engraftment in the majority of the severe Class 3 Lucarelli thalassemia patients.

Objective To determine the association between angiotensin-converting enzyme (ACE) I/D polymorphism and the presence of systemic lupus erythematosus (SLE) disease and lupus nephritis (LN), including the association with disease severity in a Thai population. Method In this retrospective study, 187 SLE patients followed up for (at least) 7 years in a rheumatology clinic of an academic hospital were enrolled. Disease severity and damage score at diagnosis and every 6 months, including treatment outcome of the first episode of LN were retrieved from medical records. The ACE genotype of SLE patients were determined by polymerase chain reaction and compared with ACE genotype in 687 controls from a database of a Thai surveillance cohort. Result There was an association between ACE I/D polymorphism and the presence of SLE disease and LN (P

To investigate the association of mitochondrial DNA (mtDNA) haplogroups and Leber hereditary optic neuropathy (LHON) in the Southeast Asian population, mtDNA haplogroup determination was performed by high-resolution restriction fragment length polymorphism in 42 patients with LHON who were carrying the G11778A mutation and in control subjects drawn from a Thai urban population unaffected by LHON. The patients with LHON were of Thai, Thai-Chinese, and Indian origin. Three mtDNA haplogroups, M, B*, and B, were found in LHON patients in a frequency similar to that in control subjects. mtDNA haplogroup F was found in none of the patients with LHON but was the second most common haplogroup in control subjects. The G11778A mutation must have arisen in our population independently from the mutation in Caucasians. In contrast to Caucasians, no specific mtDNA haplotype was associated with the patients with LHON in the Southeast Asian population. The mitochondrial polymorphisms that modify the expression of LHON in Southeast Asians could not be identified in this study. The lack of haplogroup F in our patients with LHON may indicate the protective effect of this haplogroup in the expression of this disorder.

Leber hereditary optic neuropathy (LHON) is characterized by acute or subacute bilateral visual loss, and affects mostly young males. The most common mitochondrial DNA mutation responsible for LHON worldwide is G11778A. Despite different genetic backgrounds, which are believed to influence the disease expression, most features of LHON are quite common in different populations. However, there seem to be a few ethnic-specific differences. Analyses of our 30 G11778A LHON pedigrees in Thailand showed some characteristics different from those of Caucasians and Japanese. In particular, our pedigrees showed a lower male to female ratio of affected persons (2.6:1) and much higher prevalence of G11778A blood heteroplasmy (37% of the pedigrees contained at least one heteroplasmic G11778A individual). Heteroplasmicity seemed to influence disease manifestation in our patients but did not appear to alter the onset of the disease. The estimated overall penetrance of our G11778A LHON population was 37% for males and 13% for females. When each of our large pedigrees were considered separately, disease penetration varied from 9 to 45% between the pedigrees, and also varied between different branches of the same large pedigree. Survival analysis showed that the secondary LHON mutations G3316A and C3497T had a synergistic deleterious effect with the G11778A mutation, accelerating the onset of the disease in our patients.

Purpose: To study the clinical features of Leber's hereditary optic neuropathy (LHON) in Thai patients as compared with patients in the United States, Europe, and other Asian countries. Methods: The blood mitochondrial DNA of patients from 19 Thai pedigree families was studied for LHON mutation by restriction enzyme analysis. Results: Mitochondrial mutation at nucleotide position 11778 was detected in 37 affected patients and 21 unaffected maternal relatives. Ten of the 19 families were sporadic in transmission. The male preponderance in affected patients was 76%. The onset of visual loss ranged from 6 to 53 years of age (mean = 21.5 years). Of the 31 patients whose eyes were affected bilaterally, 48.4% developed visual loss simultaneously. Unilateral visual loss was found in 2 patients but 1 already had a blind eye resulting from trauma. Onset interval between eyes was up to 12 months (mean = 2.3 months). No associated heart disease or neurological disorder was detected in our pedigrees. Hyperemic disc, retinal telangiectasia, and tortuosity of vessels appeared on ophthalmoscopy in 29% of the patients. Final visual outcome was 0.1, or worse in 82.3%, with a mean follow-up period of 19.5 months. Conclusion: The clinical features of LHON in Thai patients are similar to those found in patients harboring the 11778 mutation in the United States, Europe, and Japan. However, although there is a male predominance in all populations studied, this is not so marked in the European and Thai populations.

Department of Human Genetics, New York State Institute for Basic Research, Staten Island, New YorkThe prevalence of fragile X syndrome (FXS)is approximately 7% in Thai boys withdevelopmental delay of unknown cause. Todetermine if FXS might have a specifichaplotype association, we analyzed 125 un-related control subjects and 25 unrelatedFXS patients using 3 microsatellites,DXS548, FRAXAC1 and FRAXE, and twosingle nucleotide polymorphisms, ATL1and IVS10. FRAXAC1 and DXS548 arelocated ˘7 kb and ˘150 kb proximal to theCGG-FMR1 whereas ATL1, IVS10 andFRAXE are located ˘5.6 kb, ˘24.5 kb and˘600 kb distal to the CGG-FMR1. We found40 haplotypes in the control group and 14haplotypes in the FXS group. Of 14 haplo-types in the FXS group, 6 haplotypes werenot found in the control group suggestingpossible new mutations or admixture ofimmigrant haplotypes. We observed thatmost diverse haplotypes came from differ-ent FRAXE alleles. For this reason, weanalyzed haplotypes composed from the re-maining markers alone (DXS548-FRAXAC1-ATL1-IVS10). We found 2 major haplotypes(20-18-G-T and 20-19-A-C) with no significanthaplotype differences between the controlgroup (67/125 of 20-18-G-T and 25/125 of 20-19-A-C) and FXS group (16/25 of 20-18-G-Tand 6/25 of 20-19-A-C). The other haplotypesfound were 33/125 in the control group and3/25 in the FXS group. The two majorhaplotypes associated FXS in Thai subjectswere the two most common haplotypes inthe normal Thai subjects. We could notprove, therefore, that there were foundereffects at the FRAXA locus in Thailand. Wecould not, however, exclude it completely.These findings apparently contrast withmost other reports on FXS founder effectsin various ethnic groups.

We investigated the prevalence of a genetic variation in the factor V gene (G1691A Leiden mutation) and the prothrombin gene (G20210A) using polymerase chain reaction techniques in samples from 500 normal Thai population and among 50 unselected Thai patients with an objectively confirmed history of deep venous thrombosis. The prevalence of factor V Leiden and the prothrombin G20210A gene mutation in a group of 500 healthy controls was 0.2% in both groups (allele frequency of 0.1%). Of the 50 adult patients studied, none was a carrier of factor V Leiden or the prothrombin G20210A gene mutation. Our findings confirm that the prevalence of factor V Leiden and prothrombin G20210A gene mutation is lower among Asians than Caucasians and that the distribution of factor V Leiden is similar to that of the prothrombin G20210A variant. The low prevalence of these two mutations can, at least in part, account for the lower frequency of deep venous thrombosis reported in the Thai population. Screening for factor V Leiden and prothrombin gene mutation is of limited benefit and may not be cost-effective in Thai patients with the first episode of deep venous thrombosis.

Determine the frequency of mutations in exon 8 of ATP7B gene.The exon 8 of ATP7B gene in twenty 20 unrelated Thai patients with Wilson disease (WD) was analyzedThree heterozygous mutations were identified in four patients. The Arg778Leu (G2333T) and 2299insC mutations have been previously reported. The authors also identified a novel missense mutation, Thr766Arg (C2297G). Despite the Arg778Leu mutation being common in East Asian populations, its frequency in Thais was only 5% in the presented patients.Sequencing of the exon 8 of the ATP7B gene is insufficient for the diagnostic service testing in Thais.

Objective Osteoarthritis (OA) is a multi-factorial disease and genetic factor is one of the important etiologic risk factors. Various genetic polymorphisms have been elucidated that they might be associated with OA. Recently, several studies have shown an association between Growth Differentiation Factor 5(GDF5) polymorphism and knee OA. However, the role of genetic predisposing factor in each ethnic group cannot be replicated to all, with conflicting data in the literatures. Therefore, the aim of this study was to investigate the association between GDF5 polymorphism and knee OA in Thai population. Materials and Methods One hundred and ninety three patients aged 54-88 years who attended Ramathibodi Hospital were enrolled. Ninety cases with knee OA according to American College of Rheumatology criteria and one hundred and three cases in control group gave informed consent. Blood sample (5 ml) were collected for identification of GDF5 (rs143383) single nucleotide polymorphism by PCR/RFLP according to a standard protocol. This study protocol was approved by the Ethics Committee on human experimentation of Ramathibodi Hospital Faculty of Medicine, Mahidol University. Odds ratios (OR) and 95% confidence intervals were calculated for the risk of knee OA by genotype (TT, TC and CC) and allele (T/C) analyses. Results The baseline characteristics between two groups including job, smoking and activity were not different, except age and BMI. The entire cases and controls were in Hardy-Weinberg equilibrium (p > 0.05). The OA knee group (n = 90) had genotypic figure which has shown by TT 42.2% (n = 38), TC 45.6% (n = 41) and CC 12% (n = 11), whereas the control group (n = 103) revealed TT 32% (n = 33), TC 45.6% (n = 47), and CC 22.3% (n = 23), respectively. Genotypic TT increased risk of knee OA as compared to CC [OR = 2.41 (P = 0.04, 95%CI = 1.02-5.67)]. In the allele analysis, the T allele was found to be significantly associated with knee OA [OR = 1.53 (P = 0.043, 95%CI = 1.01-2.30)]. Conclusion These data suggested that GDF5 polymorphism has an association with knee OA in Thai ethnic. This finding also supports the hypothesis that OA has an important genetic component in its etiology, and GDF5 protein might play important role in the pathophysiology of the disease.

Background. We aimed to identify disease-predisposing variations with nevirapine-induced rash using genome-wide single-nucleotide polymorphisms (SNPs) as genetic markers. Methods. A genome-wide association study (GWAS) was performed using 550000 markers in 72 human immunodeficiency virus (HIV)‐infected Thai patients with nevirapine-induced rash and 77 nevirapine-tolerant patients, and then candidate SNPs were further evaluated in a replication set (88 patients with nevirapine-induced rash and 145 nevirapine-tolerant patients). Results. The genome-wide association analysis and replication studies of candidate SNPs identified significant associations of nevirapine-induced rash with 2 SNPs (rs1265112 and rs746647) within CCHCR1 on chromosome 6p21.3 (PGWAS 5 1.6 3 10 24 ; Preplication 5 2.6 3 10 25 ; Pcombined 5 1.2 3 10 28 ). The odds ratio (OR) of the risk genotypes under a dominant model was 4.36 (95% confidence interval [CI], 2.58‐7.36). The noncoding SNPs rs1265112 and rs746647 were in complete linkage disequilibrium with the nonsynonymous SNP rs1576 (r 2 5 1.00), which has been associated with psoriasis. The logistic regression analysis also indicated genetic variations in CCHCR1 to be significantly associated with rash, with an OR of 2.59 (95% CI, 1.82‐3.68; P 5 .007). The receiver operating characteristic curve showed that the algorithm had an area under the curve of 76.4%, which was developed with 5 factors: rs1576*G status, HLA-B*3505 status, not receiving prescribed lead-in of nevirapine, history of drug allergy, and CD4 cell count prior to the nevirapine treatment. Conclusions. We demonstrated that genetic variations in CCHCR1 are strongly associated with nevirapineinduced rash. A predictive model that includes genetic and clinical risk factors for nevirapine-associated rash might be useful in lowering the incidence of rash associated with nevirapine initiation among HIV-infected patients.

Polycyclic aromatic hydrocarbons (PAHs) are associated with an increased cancer risk. CYP1A1 and GSTs enzymes are important in metabolism of PAHs. Genetic polymorphisms of these enzymes are responsible for enzyme activity and concentration variation. The objectives of this study were to evaluate association of 1-OHP concentration with genetic polymorphisms of CYP1A1 and GSTs in Thai bus drivers. The results showed that 1-OHP levels in bus drivers were significantly higher than that in the control group. Significant difference in 1-OHP was found between smokers and non-smokers, in only bus drivers. Significantly increasing of 1-OHP levels were observed in bus drivers with CYP1A1 MspI and exon 7 variants. Whereas, bus drivers with GSTP1 Val and GSTM1 null genotypes showed decreasing in excretion of 1-OHP. No association between 1-OHP and polymorphisms of GSTT1 was found. This study indicated that 1-OHP concentrations were associated with exposure to air pollution, cigarette smoking and polymorphisms of CYP1A1, GSTM1 and GSTP1 genes.

Estrogen receptor-alpha single-nucleotide polymorphism (ER-alpha SNP) has previously shown its susceptibility to knee osteoarthritis (OA) but this association cannot be applied to ethnic groups with different genetic backgrounds.To characterize the genetic association between ER-alpha SNP and knee OA in the Thai.A case-control study was conducted at Ramathibodi Hospital from August 2007 to May 2008. Altogether, 104 cases affected by knee OA and 104 controls were included in this study. SNP rs2228480 (codon 594 G!A) on the ER-alpha gene was genotyped by a PCR-RFLP-based technique. Genotype frequencies were analyzed by logistic regression.ER-alpha SNP was normally distributed through the Hardy-Weinberg Equilibrium (HWE). The risk of knee OA was genetically associated to AG an AA genotypes compàred with homozygous wild-type GG (OR: 1.02, 95% CI: 0.60-1.80 for AG; OR: 1.27, 95% CI: 0.30-4.90 for AA).Our study showed that these genetic alterations might be associated with knee osteoarthritis in the Thai population. Further investigation on other informative SNPs on the ER-alpha gene should be performed to create a reliable haplotype that might provide a stronger link between genetic profiles and clinical picture.

BackgroundStudies on human genetic factors associated with malaria have hitherto concentrated on their role in susceptibility to and protection from disease. In contrast, virtually no attention has been paid to the role of human genetics in eliciting the production of parasite transmission stages, the gametocytes, and thus enhancing the spread of disease.Methods and findingsWe analysed four longitudinal family-based cohort studies from Senegal and Thailand followed for 2-8 years and evaluated the relative impact of the human genetic and non-genetic factors on gametocyte production in infections of Plasmodium falciparum or P. vivax. Prevalence and density of gametocyte carriage were evaluated in asymptomatic and symptomatic infections by examination of Giemsa-stained blood smears and/or RT-PCR (for falciparum in one site). A significant human genetic contribution was found to be associated with gametocyte prevalence in asymptomatic P. falciparum infections. By contrast, there was no heritability associated with the production of gametocytes for P. falciparum or P. vivax symptomatic infections. Sickle cell mutation, HbS, was associated with increased gametocyte prevalence but its contribution was small.ConclusionsThe existence of a significant human genetic contribution to gametocyte prevalence in asymptomatic infections suggests that candidate gene and genome wide association approaches may be usefully applied to explore the underlying human genetics. Prospective epidemiological studies will provide an opportunity to generate novel and perhaps more epidemiologically pertinent gametocyte data with which similar analyses can be performed and the role of human genetics in parasite transmission ascertained.

Ghosts of Selection Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme deficiency of humans, and it has been long suspected to exert an effect on Plasmodium falciparum malaria in Africa. Likewise, the increase in prevalence of the G6PD-Mahidol 487 A allele among Karen people in Thailand, who only in the past few thousand years have migrated into malarious zones, may be the result of selection by Plasmodium vivax malaria. P. vivax has recently been implicated in more severe disease than previously suspected, providing both a direct selective effect through mortality and an indirect selective effect through morbidity and reproductive failure. Louicharoen et al. (p. 1546 ) link population-genetic evidence for positive selection in an 8-year family-based study of 3000 Karen individuals and reveal that there is an association between the presence of the G6PD-Mahidol 487 A allele and a reduction in the density of P. vivax parasites circulating in the bloodstreams of infected individuals. The mutation appears to exert its effect on the physiology of immature red blood cells, which are the preferred niche for P. vivax but not of P. falciparum .

We report a 69-year-old woman who presented with dyspnea, orthopnea, and acute renal failure. She also had proximal muscle weakness suggestive of muscle disease. Her symptoms were alleviated by induced dieresis, although there was high-serum creatine kinase. Investigations for any possible etiologies of rhabdomyolysis were all negative. An X-linked recessive muscle disease was highly suspicious in view of the fact that both of her sons had suffered from muscle disease and died of respiratory failure at the ages of 22 and 29, respectively. Her muscle biopsy showed mosaic pattern with dystrophin antibody against amino-terminal, carboxy-terminal, and rod domain. Her DNA study revealed heterozygous duplication at exon 1 to 6 of the dystrophin gene as well. Therefore, she is a manifesting carrier of dystrophinopathy who was first diagnosed in late adulthood with congestive heart failure, acute episode of spontaneous rhabdomyolysis, and acute renal failure.

Investigation of a possible involvement of differences in human leukocyte antigens (HLA) in the risk of nevirapine (NVP)-induced skin rash among HIV-infected patients.A step-wise case-control association study was conducted. The first set of samples consisted of 80 samples from patients with NVP-induced skin rash and 80 samples from NVP-tolerant patients. These patients were genotyped for the HLA-A, HLA-B, HLA-C, HLA-DRB1, HLA-DQB1, and HLA-DPB1 by a sequence-based HLA typing method. Subsequently, we verified HLA alleles that showed a possible association in the first screening using an additional set of samples consisting of 67 cases with NVP-induced skin rash and 105 controls.An HLA-B*3505 allele revealed a significant association with NVP-induced skin rash in the first and second screenings. In the combined data set, the HLA-B*3505 allele was observed in 17.5% of the patients with NVP-induced skin rash compared with only 1.1% observed in NVP-tolerant patients [odds ratio (OR)=18.96; 95% confidence interval (CI)=4.87-73.44, Pc=4.6x10] and 0.7% in general Thai population (OR=29.87; 95% CI=5.04-175.86, Pc=2.6x10). The logistic regression analysis also indicated HLA-B*3505 to be significantly associated with skin rash with OR of 49.15 (95% CI=6.45-374.41, P=0.00017).A strong association between the HLA-B*3505 and NVP-induced skin rash provides a novel insight into the pathogenesis of drug-induced rash in the HIV-infected population. On account of its high specificity (98.9%) in identifying NVP-induced rash, it is possible to utilize the HLA-B*3505 as a marker to avoid a subset of NVP-induced rash, at least in Thai population.

Chronic hepatitis B is a serious infectious liver disease that often progresses to liver cirrhosis and hepatocellular carcinoma; however, clinical outcomes after viral exposure vary enormously among individuals. Through a two-stage genome-wide association study using 786 Japanese chronic hepatitis B cases and 2,201 controls, we identified a significant association of chronic hepatitis B with 11 SNPs in a region including HLA-DPA1 and HLA-DPB1. We validated these associations by genotyping two SNPs from the region in three additional Japanese and Thai cohorts consisting of 1,300 cases and 2,100 controls (combined P = 6.34 x 10(-39) and 2.31 x 10(-38), OR = 0.57 and 0.56, respectively). Subsequent analyses revealed risk haplotypes (HLA-DPA1(*)0202-DPB1(*)0501 and HLA-DPA1(*)0202-DPB1(*)0301, OR = 1.45 and 2.31, respectively) and protective haplotypes (HLA-DPA1(*)0103-DPB1(*)0402 and HLA-DPA1(*)0103-DPB1(*)0401, OR = 0.52 and 0.57, respectively). Our findings show that genetic variants in the HLA-DP locus are strongly associated with risk of persistent infection with hepatitis B virus.

Ehlers-Danlos syndrome has many subtypes. The vascular type (type IV) is characterized by thin, translucent skin, easy bruising, characteristic facial appearance, and arterial, intestinal, and/or uterine fragility.To encourage a better understanding of vascular EDS as a basis for early diagnosis, prevention, and management of complications. A first case of EDS type IV with adeno-carcinoma of the stomach in Thailand was reported and literature was reviewed.A 62-year-old Thai priest was admitted in Priest Hospital because of progressive muscle weakness of both legs with neurogenic claudication from compression fracture of L1-2. Abdominal aortic aneurysm were detected with upper gastrointestinal hemorrhage, esophagogastroduodenoscopy showed diffuse gastric body swelling and erythema resulting in chronic gastritis. Gastric biopsy was indicative of adenocarcinoma of the stomach and gastrectomy was done. Dermatologists were consulted due to generalized cutaneous pain, easy bruising following venepuncture, and EKG padding. A vascular EDS type IV was diagnosed.After gastrectomy, the patient became drowsy and unconscious from profuse recurrent cerebral hemorrhage and expired.

In the candidate gene approach, information about the distribution of single nucleotide polymorphisms (SNPs) is a crucial requirement for choosing efficient markers necessary for a case-control association study. To obtain such information, we discovered SNPs in 13 genes related to atherosclerosis by resequencing exon-flanking regions of 32 healthy Thai individuals. In total, 194 polymorphisms were identified, 184 of them SNPs, four insertions, and the rest deletions. Fifty-nine of the SNPs were characterized as novel polymorphisms, and these accounted for 30% of the identified SNPs. Comparing allele frequency distributions of the Thai population with other Asian populations shows similar patterns. In contrast, a low correlation pattern (r = 0.521) was found when comparing with either Caucasian or African populations. However, some rare alleles (rs11574541 and rs10874913) are found in the Thai population but not in other Asian populations. Most of the novel SNPs found were located outside the haplotype blocks generated by known SNPs in the Thai population. Only 5.77% of the novel SNPs lies in these defined haplotype blocks. The selection of haplotype-tagging SNPs shows that 8 of 13 genes benefited from the ethnic-specific genotype information. That is, when at least one novel SNP was present, the tagging SNPs chosen were altered. Functional prediction of 16 nonsynonymous SNPs (nsSNPs) by three different algorithm tools demonstrated that five nsSNPs possibly alter their corresponding protein functions. These results provide necessary information for conducting further genetic association studies involving the Thai population and demonstrate that resequencing of candidate genes provides more complete information for full genetic studies.

To determine the prevalence of delta-aminolevulinic acid dehydratase (ALAD) polymorphism and its effects on blood lead levels (BLLs) in Thai workers, the authors performed a cross-sectional analysis of 389 Thai workers who were exposed to lead in a battery plant. The authors collected blood for BLLs and genotypic study, and they found that the allele frequencies of ALAD1 and ALAD2 were 0.98 and 0.02, respectively. They made a comparison of BLLs between genotype by dividing the levels into 2 categories of lead exposure (high and medium magnitude of exposure) and using length of employment as a covariance. Their results showed no significant difference of BLLs between the ALAD1-1 and ALAD1-2/ALAD2-2 groups in both levels of exposure. The frequency of ALAD2 in Thai workers was low; the authors found that ALAD polymorphism had a small or only modest effect on BLLs.

Hyperhomocysteinemia was recently found to be a risk factor for stroke; however, the available data from Thailand is scarce.To study plasma homocysteine levels in ischemic stroke and compare it with age-and sex-matched controls, and to identify the association of plasma homocysteine and subtype of stroke.The authors studied plasma homocysteine levels of ischemic stroke patients with clinical signs and symptoms of stroke as confirmed by CT scan and compared them with control subjects who presented with other diseases and no clinical signs and symptoms of stroke between June 2000- May 2001 in Prasat Neurological institute. Fasting plasma homocysteine was measured by HPLC technique. Abnormal cut off point of plasma homocysteine was identified and associations of plasma homocysteine and stroke were studied by using logistic regression analyses.Two hundred and sixty-eight patients were recruited in the present study (132 controls and 136 ischemic stroke patients). The abnormal cut off point of plasma homocysteine was14 micromol/L. The authors found statically significant association of abnormal plasma homocysteine and stroke (p0.001) with odds ratio of 4.277 (95%CI 2.551-7.171). After adjusting the confounding factor the authors found that high homocysteine was significantly associated with ischemic stroke (p0.001) with odd ratio of 3.401 (95%CI 1.954-5.922). In the subgroup analyses of type of stroke and abnormal homocysteine, the authors demonstrated that abnormal homocysteine levels were more pronounced in the large vessel subtype than the small group.Abnormal homocysteine level is an independent risk factor of ischemic stroke and more correlated with large vessel subtype.

Paraoxonase (PON1) plays an important role in mechanism of organophosphorus compound (OP) toxicity, as seen both in vitro and in vivo studies. Polymorphisms of PON1 gene at coding and promoter regions have also been to affect on the hydrolytic activity and PON1 level. The objectives of this study were to determine PON1 polymorphism and activity in an OP-exposed population and the effects on inhibition of cholinesterase activity. The studied population consisted of control (n=30) and exposed groups (n=90). All enzyme activities (AChE, BuChE, paraoxonase, arylesterase and diazonase) were measured once for control group and two periods of exposure for exposed group. Three polymorphisms of PON1 (Q192R, L55M and T-108C) were identified only in the exposed subjects. The results demonstrated that AChE activity in both high (345.5 microkat/gHb) and low exposure periods (496.9 microkat/gHb) of the exposed group were significantly different from control group (649.7 microkat/gHb, p0.01). For BuChE activity, the exposed group also showed the statistically lower level in both periods (high exposure period: 62.17 microkat/L and low exposure period: 81.84 microkat/L) than those in the control group (93.35 microkat/L). Serum paraoxonase activity was significantly different among individual genotypes, RRQRRR, LLLM and -108CC-108CT-108TT, but this was not found for those of arylesterase and diazonase activities. Q192R and L55M as well as Q192R and T-108C also presented substantial linkage disequilibrium. Further analysis was performed with haplotypes and various enzyme activities. AChE activity was not affected by haplotypes. Individuals with "211" haplotype showed significantly higher paraoxonase activity and BuChE activity than other haplotypes but not in diazonase activity. In conclusion, PON1 gene exhibited a wide variation in enzyme activities both within and between genotypes which implied insights of a potentially difference in sensitivity to OP toxicity.

The similarity of the marker allele frequency and linkage disequilibrium structure between two populations are major factors for the determination of the transferability and efficiency of haplotype tagging SNP derived from one population to use for an indirect association study in another population. To prove the similarity between northern East Asian populations in Hapmap and Thais, 861 SNP in 166 drug-related genes shared between Thais, Han Chinese and Japanese were analyzed for their correlation statistics. Allele frequency, Fst statistics and linkage disequilibrium statistics (r (2)) showed a high correlation between these populations. TagSNP sets derived by an aggressive tagging algorithm from these 861 SNP in Japanese and Chinese were used to test the coverage of East Asia-derived tagSNP in Thais. TagSNP derived from Japanese and Chinese are comparable in the percentage of coverage of the alleles captured with tagSNP at r (2)or=0.8 (93% vs. 93%) in these drug-related gene loci. Additional tagSNP sets derived from the combination of Japanese- and Chinese-derived tagging SNP sets were used to test the coverage in Thais. The later set improved the percentage of coverage of alleles captured with tagSNP at r (2)or=0.8-98% for these sites. High similarity between Thais and northern East Asian allele frequency and linkage disequilibrium statistics supported that tagSNPs derived from the northern East Asian population should be useful for an indirect association study in Thais. The combination of non-overlapping Japanese derived tagSNP and Chinese-derived tagSNP improved the percentage of genomic coverage in Thais, at least in these drug-related gene loci.

There has been controversy whether oculopharyngodistal myopathy (OPDM) commonly seen in Japan is a distinct disease entity or a variant of oculopharyngeal muscular dystrophy (OPMD) initially described in French-Canadians and has since been reported in other ethnic groups. Both diseases have autosomal dominant inheritance and OPDM patients are clinically similar to OPMD with slowly progressive ptosis, ophthalmoplegia and dysphagia except that most of the former usually have distal as opposed to proximal weakness and most of them are genetically different from the latter The authors report here 2 siblings with clinical features of OPDM. This entity is rare outside Japan and this is the first family to be reported from Thailand

Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active gamma-globin gene expression leads to elevated fetal hemoglobin (Hb F) levels in adult life [Stamatoyannopoulos G, Grosveld F. Hemoglobin switching. In: Stamatoyannopoulos G, Majerus PW, Perlmutter RM, Varmus H, eds. The Molecular Basis of Blood Diseases. Philadelphia: W.B. Saunders, 2001:135-182; Wood WG. Hereditary persistence of fetal hemoglobin and delta(beta) thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press, 2001:356-388; and Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publishers, 1981:450-507]. The condition is caused either by mutation of the beta- and gamma-globin genes, or the gamma-gene controlled region on other chromosomes. Several families with this condition have been reported from Vietnam, Cambodia and China, and the Southeast Asian mutation (or HPFH-6), a 27 kb deletion, was demonstrated. Here we report on a mother and her daughter of the Karen ethnic group with high levels of Hb F, living in the Suan Pueng District on the border of Thailand and Myanmar. Genotyping showed a heterozygosity for the 27 kb deletion of the beta-globin gene. Their conditions have been confirmed by gap polymerase chain reaction (PCR) with three oligonucleotide primers recently developed by Xu et al. [Xu X-M, Li Z-Q, Liu Z-Y, Zhong X-L, Zhao Y-Z, Mo Q-H. Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with beta-thalassemia in a Chinese family. Am J Hematol 2000; 65:183-188.], and a DNA sequencing method. Thus far there has been no official report of the HPFH-6 anomaly from Thailand. The compound heterozygosity of beta-thalassemia (thal) and hereditary persistence of Hb F causes the phenotype of thalassemia intermedia; in contrast, homozygotes for this anomaly show only mild microcytic anemia. Hence, genetic counseling for hereditary persistence of Hb F carriers is needed for family planning.