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Symptomatic remediation from attention deficit hyperactivity disorder (ADHD)-associated traits is achieved by treatment with methylphenidate (MPH)/atomoxetine (ATX). We have analyzed the association of functional CYP2D6 variations, rs1065852, rs3892097, rs1135840, and rs1058164, with ADHD in the Indian subjects. Subjects were recruited following the Diagnostic and Statistical Manual for Mental Disorders. Trait scores were obtained from the Conner's Parents Rating Scale-Revised. After obtaining informed consent, blood was collected for DNA isolation, and genotyping was performed by PCR or TaqMan-based methods. Probands were treated with MPH or ATX based on age, symptoms, and drug availability. Treatment outcome was assessed using a structured questionnaire. Data obtained was analyzed to identify the association of CYP2D6 variations and the SLC6A3 rs28363170 with the treatment outcome. The frequency of rs1135840 "G" and rs1065852 "G" was higher in the male ADHD probands. Bias in parental transmission (p=0.007) and association with higher trait scores were observed for rs1065852 "A". Independent influence of rs1065852 on ADHD was also observed. Probands carrying rs1065852 'GG', rs1135840 'CG', and rs28363170 10R exhibited significant symptomatic improvement with MPH, while probands with rs1135840 'CC' and rs28363170 9R showed improvement after ATX treatment. ADHD probands having specific CYP2D6 genetic variations respond differentially to pharmaceutical intervention. [ABSTRACT FROM AUTHOR]

Abstract Background Proper expression and functioning of transcription factors (TFs) are essential for regulation of different traits and thus could be crucial for the development of complex diseases. Subjects with Down syndrome (DS) have a higher incidence of acute lymphoblastic leukemia (ALL) while solid tumors, like breast cancer (BC) and oral cancer (OC), show rare incidences. Triplication of the human chromosome 21 in DS is associated with altered genetic dosage of different TFs. V-ets erythroblastosis virus E26 oncogene homolog 2 (ETS2) and Single Minded 2 (SIM2) are two such TFs that regulate several downstream genes involved in developmental and neurological pathways. Here we studied functional genetic polymorphisms (fSNP) in ETS2 and SIM2 encoding genes in a group of patients and control subjects to better understand association of these variants with DS phenotypes. Methods We employed an in silico approach to identify potential target pathways of ETS2 and SIM2. fSNPs in genes encoding for these two TFs were identified using available databases. Selected sites were genotyped in individuals with DS, their parents, ALL, BC, OC as well as ethnically matched control individuals. We further analyzed these data by population-based statistical methods. Results Allelic/genotypic association analysis showed significant (P Conclusions We infer from the present investigation that the difference in frequencies of fSNPs and their independent as well as interactive effects may be the cause for altered expression of SIM2 and ETS2 in DS and malignant groups, which affects different downstream biological pathways. Thus, altered expression of SIM2 and ETS2 could be one of the reasons for variable occurrence of different malignant conditions in DS.

Objectives: Proper metabolism of the folate is crucial for maintaining DNA integrity, chromosome structure, methylation, as well as gene expression, and thus, folate is speculated to contribute to the etiology of different disorders. Since the etiology of autism spectrum disorder (ASD) is believed to be influenced by both genetic and environmental factors, we hypothesized that functional single nucleotide polymorphisms (SNPs) affecting folate metabolic pathway may have a causal role in the etiology of ASD. Methods: We analyzed three SNPs, rs2071010, rs2298444 and rs1801198 (in the folate receptor 1, folate receptor 2 and transcobalamin 2, respectively), in 867 ethnically matched subjects including 206 ASD probands and 286 controls. Plasma vitamin B6 and folate were measured in age-matched probands and controls. Results: ASD probands showed a higher frequency of rs2298444 'A' allele (P = 0.01) and genotypes with 'A' allele (P = 0.03) when compared with the controls. rs1801198 'C' allele and 'CG' genotype also showed higher occurrence in the probands (P = 0.009 and 0.005, respectively). Gender-based stratified analysis revealed a significant higher frequency of rs2298444 'A' allele (P = 0.003), genotypes with rs2298444 'A' allele (P = 0.003) and rs1801198 CG (P = 0.001) in the male probands. Studied variants also showed statistically significant associations with ASD-associated traits measured by the Childhood Autism Rating Scale. ASD subjects exhibited gross deficiency in vitamin B6 level when compared with age-matched controls (P < 0.001), which correlated with risk genetic variants. Discussion: We infer from this pioneering study on eastern Indian subjects that vitamin B6 deficiency, along with risk gene variants, may affect ASD-associated symptoms, warranting further investigation in large cohorts. [ABSTRACT FROM AUTHOR]

Abstract Background Cystathionine β-synthase (CBS) mediates conversion of homocysteine to cystathionine and deficiency in enzyme activity may lead to hyperhomocysteinemia/homocystinuria, which are often associated with mental retardation (MR). A large number of polymorphisms have been reported in the CBS gene, some of which impair its activity and among these, a T833C polymorphism in cis with a 68 bp insertion at 844 in the exon 8 is found to be associated with mild hyperhomocysteinemia in different ethnic groups. Methods The present study is aimed at investigating the association between T833C/844ins68 polymorphism and MR. One hundred and ninety MR cases were recruited after psychometric evaluation. Hundred and thirty-eight control subjects, two hundred and sixty-seven parents of MR probands and thirty cardiovascular disorder (CVD) patients were included for comparison. Peripheral blood was collected after obtaining informed written consent. The T833C/844ins68 polymorphism was investigated by PCR amplification of genomic DNA and restriction fragment length polymorphism analysis, followed by statistical analysis. Results The genotypic distribution of the polymorphism was within the Hardy-Weinberg equilibrium. A slightly increased genotypic frequency was observed in the Indian control population as compared to other Asian populations. Both haplotype-based haplotype relative risk analysis and transmission disequilibrium test reveled lack of association of the T833C/844ins68 polymorphism with MR; nevertheless, the relative risk calculated was higher (>1) and in a limited number of informative MR families, preferential transmission of the double mutant from heterozygous mothers to the MR probands was noticed (χ2 = 4.00, P < 0.05). Conclusion This is the first molecular genetic study of CBS gene dealing with T833C/844ins68 double mutation in MR subjects. Our preliminary data indicate lack of association between T833C/844ins68 polymorphism with MR. However, higher relative risk and biased transmission of the double mutation from heterozygous mothers to MR probands are indicative of a risk of association between this polymorphism with mental retardation.

Opioid receptor mu1 (OPRM1) is the target of many opioid drugs, and it is known to have affinity toward both endogenous and exogenous opioids, opiate and opioid analgesic drugs. The present study was undertaken to explore association of single nucleotide polymorphisms (SNPs) in the OPRM1 gene with heroin use disorder. Ten OPRM1 polymorphisms were analyzed in 132 cases and 147 healthy controls. The SNP rs483481 showed significant allelic, genotypic and haplotypic association (Allelic: p-value = 0.003, OR = 1.75, CI = 1.21-2.55) (Genotypic: p-value = 0.003, OR = 1.72, CI = 1.08-2.75) with heroin use disorder. Allelic and genotypic association remained significant even after multiple testing corrections with 1000 permutations. A significant positive correlation between 'Number of times drug abstained' and 'rs483481-AA genotype' (p-value = 0.002; Pearson correlation = 0.265) was also observed. One-way ANOVA analysis demonstrated significant association of rs483481 with 'number of times drug abstained' (F = 4.86, p-value =0.009). 'A' allele and 'AA' genotype of marker rs483481 seem to confer protective effect while 'G' allele and 'GG' genotype potentiates risk for heroin use disorder. OPRM1 is found to be associated with heroin use disorder in the studied Manipuri cohort. The study suggests that individuals with G allele and GG genotypes at rs483481 could be more vulnerable to heroin dependence, and it could be taken into consideration in prevention and intervention programs. [ABSTRACT FROM AUTHOR]

Platelet hyperserotonemia in a subset of Autism Spectrum Disorder (ASD) probands, efficacy of selective serotonin reuptake inhibitors (SSRIs) in reducing behavioral deficits and gender-bias in normal serotonin (5-hydroxy tryptamine or 5-HT) synthesis suggest disruption in stringent regulation of serotonin metabolism in ASD. Therefore, we investigated the changes in 5-HT and 5-hydroxy indole acetic acid (5-HIAA) in ASD probands to assess its effect on the behavior of male and female probands. ASD cases (n = 215) were examined using childhood autism rating scale (CARS). Platelet 5-HT (104 cases and 26 controls) and platelet/plasma 5-HIAA (73 cases and 17 controls) were estimated using high performance liquid chromatography coupled with electrochemical detector (HPLC-ECD). In male probands, we observed increase in platelet 5-HT content in association with increase in the score for adaptive responses and increase in platelet 5-HIAA levels with concomitant decline in the score for intellectual response. Age did not influence the neurochemical parameters, but imitation, listening responses and nonverbal communication scores decreased with age. Conversely in female probands, plasma 5-HIAA level significantly attenuated with age, when platelet 5-HT content remained unchanged. Interestingly, platelet/plasma 5-HT and plasma 5-HIAA were higher in female controls. Female probands displayed severe autism-associated behaviors. Overall results indicate gender-bias in 5-HT and 5-HIAA regulation, which probably increases the threshold level of ASD phenotypes in the females, thereby affecting ASD prevalence in a sex-specific manner. [ABSTRACT FROM AUTHOR]

Organizational inefficiency and inattention are speculated to be the reason for executive deficit (ED) of ADHD probands. Even with average IQ, probands often perform poorly due to higher inattention. Pharmacotherapy, cognitive behavioural therapy, and counselling provide only symptomatic relief. Several candidate genes showed involvement with ADHD; the most consistent are dopamine receptor 4 (DRD4) and solute carrier family 6 member 3 (SLC6A3). We analyzed association of rarely investigated DRD4 and SLC6A3 variants with ADHD core traits in Indo-Caucasoid probands. ED, inattention, organizational efficiency, and IQ were measured by Barkley Deficit in Executive Functioning-Child & Adolescent scale, DSM-IV-TR, Conners' Parent Rating Scale-revised, and WISC respectively. Target sites were analyzed by PCR, RFLP, and/or Sanger sequencing of genomic DNA. DRD4 variants mostly affected inattention while SLC6A3 variants showed association with IQ. Few DRD4 and SLC6A3 variants showed dichotomous association with IQ and inattention. DRD4 Exon3 VNTR >4R showed negative impact on all traits excepting IQ. Inattention showed correlation with attention span, organizational efficiency, and ED, while IQ failed to do so. We infer that IQ and attention could be differentially regulated by dopaminergic gene variants affecting functional efficiency in ADHD and the two traits should be considered together for providing better rehabilitation. [ABSTRACT FROM AUTHOR]

Byline: Samikshan. Dutta, Jyoti. Shaw, Swagata. Sinha, Kanchan. Mukhopadhyay Chromosomal abnormalities are thought to be the most common cause of mental retardation (MR). However, apart from a few selected types [...]

Byline: Samikshan. Dutta, Aneek. Das, Kanchan. Mukhopadhyay Sir, Down syndrome (DS) well known for trisomy of the 21[sup] st chromosome (MIM 190685) is a complex genetic disorder with prevalence of [...]

Byline: Nipa. Bhaduri, Manali. Das, Aneek. Das, Kanchan. Mukhopadhyay Background: A 48bp variable number of tandem repeat (VNTR), in the dopamine receptor D4 ( DRD4 ), has been extensively studied [...]

Background: Attention deficit hyperactivity disorder (ADHD) is an etiologically complex childhood onset neurobehavioral disorder characterized by age-inappropriate inattention, hyperactivity, and impulsivity. Symptom severity varies widely and boys are diagnosed more frequently than girls. ADHD probands were reported to have abnormal transmissions of dopamine, serotonin, and/or noradrenaline. Monoamine oxidase A (MAOA) and B (MAOB), mitochondrial outer membrane bound two isoenzymes, mediate degradation of these neurotransmitters and thus regulating their circulating levels. Case-control analyses in different populations, including Indians, suggested involvement of MAOA and MAOB genes in the etiology of ADHD. Due to high heritability rate of ADHD, we tested familial transmission of MAOA and MAOB variants to ADHD probands in 190 nuclear families having ADHD probands from Indo-Caucasoid ethnicity. Methods: Subjects were recruited following the Diagnostic and Statistical Manual of Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioral traits in probands. Genotyping was performed through PCR-based amplification of target sites followed by DNA-sequencing and/or gel-electrophoresis. Data obtained were analyzed by family based statistical methods. Results: Out of 58 variants present in the analyzed sites only 15 were found to be polymorphic (30 bp-uVNTR, rs5906883, rs1465107, rs1465108, rs5905809, rs5906957, rs6323, rs1137070 from MAOA and rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324, rs3027440 from MAOB). Statistically significant maternal transmission of alleles to male probands was observed for MAOA rs5905809 'G' (p = 0.04), rs5906957 'A' (p = 0.04), rs6323 'G' (p = 0. 0001) and MAOB rs56220155 'A' (p = 0.002), rs2283728 'C' (p = 0.0008), rs2283727 'C' (p = 0.0008), rs3027441 'T' (p = 0.003), rs6324 'C' (p = 0.003), rs3027440 'T' (p = 0.0002). Significantly preferential maternal transmissions of different haplotype combinations to male probands were also noticed (p < 0.05), while female probands did not reveal such transmission bias. Behavioral traits of male probands exhibited significant association with gene variants. Age of the mother at pregnancy also revealed association with risk variants of male probands. Conclusions: It may be inferred that the MAOA and MAOB variants may contribute to the etiology of ADHD in the Indo-Caucasoid population and could be responsible for higher occurrence of ADHD in the boys. [ABSTRACT FROM AUTHOR]

The objective was to investigate contribution of the dopamine receptor 5 (DRD5) gene variants in the symptoms of attention-deficit/hyperactivity disorder (ADHD) probands since brain regions identified to be affected in these group of patients have higher expression of the DRD5 receptor. Out of 22 exonic variants, 19 were monomorphic in the Indo-Caucasoid individuals. rs6283 “C” and rs113828117 “A” exhibited significant higher occurrence in families with ADHD probands. Several haplotypes showed biased occurrence in the probands. Early and late onset groups exhibited significantly different genotypic frequencies. A new G>A substitution was observed in the control samples only. The late onset group exhibited higher scores for hyperactivity as compared to the early onset group. The authors infer that the age of onset of ADHD may at least partially be affected by DRD5 variants warranting further investigation on the role of DRD5 in the disease etiology. [ABSTRACT FROM AUTHOR]

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention, excessive motor activity and impulsivity detected mostly during childhood. These traits are known to be controlled by monoamine neurotransmitters, chiefly dopamine, serotonin and norepinephrine. Monoamine oxidase A (MAOA) and B (MAOB), two isoenzymes bound to the outer membrane of mitochondria, are involved in the degradation of monoamines and were explored for association with ADHD in different ethnic groups. In the present study, few exonic as well as intronic MAOB variants were analyzed in ADHD probands (N = 150) and ethnically matched controls (N = 150) recruited following the Diagnostic and Statistical Manual for Mental Disorders-4th edition (DSM-IV). Appropriate scales were used for measuring the behavioural attributes. Gene variants were analyzed by amplification of target sites followed by DNA sequencing and data obtained were analyzed by population based statistical methods. Results: Out of 34 variants present in the analyzed sites, only seven functional variants, rs4824562, rs56220155, rs2283728, rs2283727, rs3027441, rs6324 and rs3027440, were found to be polymorphic. rs2283728 ‘C’ (P = 3.45e-006) and rs3027440 ‘T’ (P = 0.02) alleles showed higher frequencies in ADHD probands as compared to controls. rs56220155 ‘A’ (P = 0.04) allele and ‘GA’ (P = 0.04) genotype showed higher frequencies in the male and female ADHD probands respectively as compared to sex-matched controls. Analysis of pairwise linkage disequilibrium revealed striking differences between probands and controls. Haplotype analysis revealed significantly higher occurrence of different haplotypes in the ADHD probands while some haplotypes were detected in the controls only. Higher scores for conduct problems were found to be associated with rs56220155 ‘A’ (P = 0.05) allele in the male ADHD probands. Multifactor dimensionality reduction analysis showed independent as well as interactive effects of polymorphic variants which were more robust in the male probands. Conclusions: Since all the polymorphic variants analyzed were functional, it may be inferred that MAOB gene variants are contributing to the etiology of ADHD in the Indo-Caucasoid population from eastern India which merits further in depth analysis. [ABSTRACT FROM AUTHOR]

Contribution of genes in attention deficit hyperactivity disorder (ADHD) has been explored in various populations, and several genes were speculated to contribute small but additive effects. We have assessed variants in four genes, DDC (rs3837091 and rs3735273), DRD2 (rs1800496, rs1801028, and rs1799732), DRD4 (rs4646984 and rs4646983), and COMT (rs165599 and rs740603) in Indian ADHD subjects with comorbid attributes. Cases were recruited following the Diagnostic and Statistical Manual for Mental Disorders-IV-TR after obtaining informed written consent. DNA isolated from peripheral blood leukocytes of ADHD probands (N = 170), their parents (N = 310), and ethnically matched controls (n = 180) was used for genotyping followed by populationand family-based analyses by the UNPHASED program. DRD4 sites showed significant difference in allelic frequencies by casecontrol analysis, while DDC and COMT exhibited bias in familial transmission (P < 0.05). rs3837091 "AGAG," rs3735273 "A," rs1799732 "C," rs740603 "G," rs165599 "G" and single repeat alleles of rs4646984/rs4646983 showed positive correlation with comorbid characteristics (P < 0.05). Multi dimensionality reduction analysis of case-control data revealed significant interactive effects of all four genes (P < 0.001), whilefamily-baseddatashowedinteractionbetweenDDCandDRD2(_P = 0.04). This first study on these gene variants in Indo-Caucasoid ADHD probands and associated co-morbid conditions indicates altered dopaminergic neurotransmission in ADHD. [ABSTRACT FROM AUTHOR]

Trisomy of the 21{st} chromosome leads to an over dosage of several regulatory genes in Down syndrome (DS). Though allelic and genotypic combinations formed between genes are interesting, till date, this particular area has never been explored in DS. In the present investigation four SNPs in two transcription factors, Single minded 2 (SIM2) and V-ets erythroblastosis virus E26 oncogene homolog2 (ETS2), located in the 21{st} chromosome were genotyped to understand their role in DS. Genomic DNA of eastern Indian probands with DS (N=132), their parents (N=209) and ethnically matched controls (N=149) was subjected to PCR-based analyses of functionally important SNPs followed by statistical analyses. ETS2 rs461155 showed high heterozygosity in DS. Significantly lower frequency of SIM2 C-G haplotype (rs2073601-rs2073416) was noticed in individuals with DS (P value =0.01669) and their fathers (P value=0.01185). Significantly lower frequency of the A-C-C-G with higher frequency of A-C-A-G haplotypes was also noticed in subjects with DS (P value =0.02089 and 0.00588 respectively). Data obtained indicate that the rs2073601 'A' allele, responsible for nonsynonymous substitution of leucine to methionine, may have some role in DS in this population. [ABSTRACT FROM AUTHOR]

Different components of the folate metabolic cycle are crucial for maintaining integrity of DNA. The present study was aimed at exploring the role of some important constituents of the folate cycle in the etiology of idiopathic intellectual disability (IID). Nuclear families with IID probands (n = 226) and ethnically matched controls (n = 181) were recruited for micronucleus, karyotype, genetic polymorphism (MTR rs1805087, MTRR rs1801394, and DHFR rs70991108), folate, vitamin B6, vitamin B12, and cysteine analysis. Significant difference in genotype frequencies in IID probands and their parents were observed for rs1805087 (P = 0.03, 0.02), rs1801394 (P = 0.03, 0.001), and rs70991108 ((P = 0.03, 0.02) as compared to controls. IID probands showed significantly higher micronucleus frequency (P = 0.01) and decreased vitamin B6 level (P = 0.002). A strong correlation between rs1801394 'G' allele and micronucleus was also noticed. From the present investigation, a role of genetic polymorphisms and vitamin B6 levels could be hypothesized in the etiology of IID. [ABSTRACT FROM AUTHOR]

In India as well as in other South Asian countries study of food and food related behaviour has often been dominated by the economic discourses on production and distribution. The scope of anthropological study of food has generally remained rather narrow and restricted to enquiries into nutritional status of populations. Only occasionally ethnography of production, distribution, processing and consumption of food has found some place in the works of the anthropologists. In some parts of the world, especially in Western Europe and North America, studies related to anthropology of food took off in late nineteenth century. Since then it has remained engaged in all the major movements of theoretical anthropology. The Indian scenario has changed to some extent in recent years; critical observations and comments on several important and prospective subjects ranging from food security, power relations centring production, distribution and consumption of food, varied facets of public culture and traditional knowledge systems related to food and beverage have been made. Still, the varied foodscape of the country calls for well designed and sustained study programmes, which would look into the following aspects: 1) Cognitive categorization of food and beverage and its rationale. This would include the categories of 'traditional' and 'non-traditional'; 2) Beliefs and practices related to production, procurement, processing and consumption of food and beverage; 3) Beliefs and practices related to sharing of food and beverage across age-group, gender, marital status, jati and religious boundaries; 4) Food and beverage eaten or avoided during religious and festive occasions, life cycle rituals. Why some foods are sacred and others profane; 5) Variation across social and economic strata as well as across space in use of different ingredients like oil and spices. Reasons offered to justify the variations; 6) Material culture of food and beverage; utensils, hearth, eating space, furniture, variation between gender, age, groups of insiders and outsiders with respect to the above items; 7) Categories of contamination; what are the contaminating agents and how those can be removed or mitigated; 8) Documentation of the medicinal properties of food and beverage, both preventive and curative; and 9) The written and oral traditions related to food require to be documented. [ABSTRACT FROM AUTHOR]

Background: Congenital pouch colon, also known as congenital short colon or "Pouch colon syndrome", is a rare condition that occurs in association with anorectal malformations; colon is either partially or completely replaced by pouch-like dilatation and communicates with the urogenital tract by means of a fistula. This anomaly is exclusively seen in Northern parts of India with only a few cases reported from elsewhere. Case Presentation: A 1-day old neonate was presented with abdominal distension due to lack of passage of meconium. Clinical and radiological investigations revealed ano-rectal malformation. Incidental findings were left sided renal agenesis and right sided anorchia. Laparotomy revealed congenital pouch colon which was dealt accordingly. The baby is now healthy and awaiting further reconstructive surgery. Conclusion: Although urogenital anomalies are not uncommon with congenital pouch colon, the finding of renal agenesis with unilateral anorchia is quite rare. [ABSTRACT FROM AUTHOR]

The Ang, one of the three groups of people representing the Little Andamanese group of the Andaman Islands are popularly known as Jarawas. Sustained non-hostile interaction between the Ang and the settler communities became more frequent since late 1990s. The territory presently under Ang occupation, notified as Jarawa Reserve in 1957, was not inhabited by them even one and half century back. Since the days of colonisation, the Ang habitat was subjected to different kinds of colonial activities. It has been observed n the recent years that the band groups among the Ang are not permanent; those are subjected to fission and fusion a few times each year. The entire territory under Ang occupation is divided into three smaller territories. It has been noted that the band or territorial groups do not regulate marriage. The Ang forage both terrestrial and aquatic resources for food and non-food necessities, but their dependence on terrestrial resources is more. While hunting is primarily a male activity, both men and women do fishing. Gathering is a bisexual activity; females have been found to spend more time than males in gathering activities. Comparing the contemporary Ang social division with the Great Andamanese society of yesteryears one might notice remarkable resemblances. However, structure and function of the Ang territorial groups are different from the Great Andamanese septs and Onge territorial clans. It has been observed, in spite of sustained and intensive contact with the settler communities in recent years, the Ang have not accepted the cultural traits of the settlers uniformly or permanently. [ABSTRACT FROM AUTHOR]

Plasma dopamine β-hydroxylase activity (plDβH) is tightly regulated by the DBH gene and several genetic polymorphisms have been found to independently exert their influence. In the present investigation, association of four DBH polymorphisms, DBH-STR, rs1611115, rs1108580, and rs2519152 with plDβH was examined in blood samples from 100 unrelated individuals belonging to the state of West Bengal, Eastern India. Genotypes obtained after PCR amplification and restriction digestion were used for statistical analyses. plDβH was measured using a photometric assay and its correlation with the genetic polymorphisms was analyzed using analysis of variance and linear regression. Moderate linkage disequilibrium (LD) was observed between DBH-STR and rs1611115, while rs1108580 and rs2519152 were in strong LD. 'T' allele of rs1611115 showed strong negative correlation with plDβH, whereas DBH-STR, rs1108580 and rs2519152 had no major effect. Four haplotypes showed significant influence on plDβH. This is the first report on the effect of genetic polymorphisms on plDβH from the Indian sub-continent. rs1611115 was the only polymorphism that showed substantial control over plDβH. Other polymorphisms which did not show individual effects could possibly be part of larger haplotype blocks that carry the functional polymorphisms controlling plDβH. [ABSTRACT FROM AUTHOR]

Although genetic, nutritional, and environmental factors have been found to aggravate mental retardation in ∼1% of individuals, no cause is known till date. In this study, two genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR), C677T (rs#1801133) and A1298C (rs#1801131), have been investigated in idiopathic mental retardation (IMR) subjects. Significantly higher frequency of the C677 allele was observed in IMR (n = 155; χ2 = 5.5; P = 0.019) and moderate IMR (n = 67; χ2 = 6.16; P = 0.013) groups as compared to controls (n = 126); for A1298C, no significant difference was noticed. TDT analysis revealed preferential transmission of C677 allele to a small group of mild IMR probands (χ2 = 5.545; P = 0.018). Higher frequency of CA haplotype was also noticed in IMR cases as compared to controls (χ2 = 6.28; P = 0.012). We infer from the present investigation that these polymorphisms are not contributing to the aetiology of IMR in this population since both case-control and family-based analysis revealed no significant transmission of the mutated allele. [ABSTRACT FROM AUTHOR]

Abstract: Recent trends in medications for attention deficit hyperactivity disorder (ADHD) suggest that norepinephrine (NE) deficiency may contribute to the disease etiology. Dopamine beta hydroxylase (DBH) is the key enzyme which converts dopamine to NE and since DBH gene is considered a major quantitative trait locus for plasma DBH activity, genetic polymorphism may lead to altered NE neurotransmission. Several polymorphisms including a 5′ flanking −1021C→T polymorphism, was reported to be associated with changed DBH activity and an association between −1021C→T polymorphism with ADHD was observed in Han Chinese children. We have carried out family-based studies with three polymorphisms in the DBH gene, −1021C→T polymorphism, exon 2*444g/a and intron 5 TaqI RFLP, to explore their association with Indian ADHD cases. Allele and genotype frequency of these polymorphisms in ADHD cases were compared with that of their parents and a control group. Haplotypes obtained were analyzed for linkage disequilibrium (LD). Haplotype-based haplotype relative risk analysis and transmission disequilibrium test showed lack of significant association between transmission of the polymorphisms and ADHD. A haplotype comprising of allele 1 of all polymorphisms showed a slight positive trend towards transmission from parents to ADHD probands. Strong LD was observed between *444g/a and TaqI RFLP in all the groups. However, low D′ values and corresponding log of odds scores in the control group as compared to the ADHD families indicated that, the incidence of the two polymorphisms being transmitted together could be higher in ADHD families. [Copyright &y& Elsevier]