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Genetic association studies have linked a number of single nucleotide polymorphisms (SNPs) with unconjugated hyperbilirubinemia. The present study was undertaken to validate the association of SNPs with development of hyperbilirubinemia in Indian neonates. Genotyping of five SNPs in two candidate genes was performed in 126 infants with hyperbilirubinemia and 181 controls by PCR-RFLP, Gene Scan analysis and direct DNA sequencing. Genetic polymorphisms of the UGT1A1 promoter, specifically the -3279 T➔G phenobarbital responsive enhancer module (rs4124874) and (TA)7 dinucleotide repeat (rs8175347) as well as the coding region variants (rs2306283 and rs4149056) of the OATP2 gene were significantly higher among the cases than the controls. The presence of the mutant haplotypes either in homozygous, heterozygous or compound heterozygous state had a significant effect on neonatal hyperbilirubinemia as well as on the requirement of phototherapy than those with the wild haplotype. Further, a significantly higher number of hyperbilirubinemic cases had ≥3 variants than the controls (73.80% vs 40.36%, p<0.0001) and the mean total serum bilirubin levels and requirement of phototherapy also increased according to the number of variants co-expressed. This study demonstrates that UGT1A1 and OATP2 polymorphisms were associated with altered bilirubin metabolism and could be genetic risk factors for neonatal hyperbilirubinemia. [ABSTRACT FROM AUTHOR]

Abstract: Several single nucleotide polymorphisms of the TP53 gene have been reported, amongst which polymorphism in codon 72 (rs1042522) has received significant attention and shown to be associated with disease susceptibility in different cancer types. However, there are variable reports on this polymorphism in gliomas from worldwide with inconsistent results. In addition, the implications of other polymorphic loci are not much explored in gliomas. Hence, in the present study the TP53 sequence was analyzed for all polymorphism and mutations in a total of 84 gliomas of different types and grades from patients of Indian origin. The complete sequence of all coding exons (2 to 11) and introns 2, 3, 5 and 8 of TP53 gene were studied while for introns 1, 4, 6, 7, 9 and 10, only exon flanking regions could be studied. The polymorphic loci were compared with control population. In addition to the well known codon 72 polymorphism (rs1042522), three other polymorphisms rs1642785, rs1800370 and a 16 base pair insertion in intron-3 were found. At codon 72, our study showed higher Arg/Arg genotype in gliomas compared to normal population (38% versus 13%). The Arg allele frequency in glioma patients was comparatively higher than controls (0.55 versus 0.45; P=0.037). The Arg allele frequency was also high in adult glioblastomas compared to paediatric counterparts (0.55 versus 0.36). However, there was no significant association of TP53 mutations with any genotype of codon 72. At rs1642785, the G allele frequency was significantly higher in gliomas than in control population (0.55 versus 0.36, P=0.005). The genotype at a 16 base pair insertion in intron-3 was almost similar in case and control. However, the polymorphism at rs1800370 was exclusive to gliomas. This is the first report of TP53 gene polymorphism in glioma patients from India. Our study also delineates the frequency of four polymorphisms in gliomas for the first time. The codon 72 variant (rs1042522) and rs1642785 polymorphisms possibly poses risk to glioma development in Indian population. However, the functional significance of these polymorphism needs further elucidation. [Copyright &y& Elsevier]

Background: Obstructive sleep apnea (OSA) is prevalent in 7.5% in urban Asian Indians. Peroxisome proliferator activated receptor gamma2 (PPARγ2) has been implicated in adipocyte differentiation. Neuropeptide Y (NPY) is also considered as a candidate gene for excess body fat accumulation. The association of PPARγ2 (Pro12Ala)} and NPY (Leu7Pro) gene polymorphisms with OSA has not been studied in Asian Indians. Objective: To study the distribution of PPARγ2 (Pro12Ala) and NPY (Leu7Pro) polymorphism in Asian Indians with and without OSA. Methods and results: This study was carried out in 252 obese subjects [(body mass index (BMI > 25 kg/m^{2})]; 142 with OSA and 110 without OSA. Measurements included anthropometric and biochemical parameters (fasting blood glucose, lipid profile, various circumferences and skin-fold thicknesses). PPARγ2 (Pro12Ala) and NPY (Leu7Pro) gene} polymorphisms were studied in all subjects. The frequency of the variant allele (Ala12) of PPARγ2 gene was significantly higher in subjects with OSA (14.4%) when compared with subjects without OSA (5.5%; χ^{2}= 9.7; p = 0.001). The distribution of the variant allele (Pro7) of NPY gene was comparable in subjects with OSA (3.5%) and without OSA (3.6%; χ ^{2} = 0.001, p = 0.94). Conclusion: This study reveals a significantly higher frequency of PPARγ2 (Ala12) allele in obese Asian Indians with OSA when compared to obese Asian Indians without OSA. [ABSTRACT FROM AUTHOR]

Abstract: The prevalence of thiopurine S-methyltransferase (TPMT) polymorphism and its association with clinical and hematological toxicities was retrospectively analyzed in 71 Indian children with acute lymphoblastic leukemia (ALL). Only heterozygous TPMT alleles were observed (10%, 7/71) with relative frequencies being *1/*3C (4.2%), *1/*2 (4.2%) and *1/*3A (1.4%). The median 6-mercaptopurine dose administered during the maintenance therapy was 31% lower among patients with heterozygous TPMT alleles versus the rest (32.1mg/m2/day and 46.2mg/m2/day, p =0.005), though the myelosuppression and toxicities were similar in both the groups. Identification of TPMT genotype appears to be important in making the ALL treatment more effective and less toxic. [Copyright &y& Elsevier]

The association between apolipoprotein E (apo E) polymorphism and stroke has been controversial. So far there are no studies reported on the polymorphism of apolipoprotein E in cerebrovascular diseases in the Asian Indians. A blinded case–control study was therefore undertaken and the apo E genotypes and lipid profile of a total of 120 subjects (63 stroke patients and 57 healthy controls) were done. The frequency distribution of apo E alleles and genotypes were assessed and their relation with the occurrence of stroke in Asian Indian subjects was determined. A significantly high frequency of apo ε4 allele (30%) was observed in the stroke patients than the controls (11%) (p < 0.005), and patients with ε4 allele had a fourfold higher odds to develop stroke OR (95%CI) 4.2 (1.8–10.1) (p < 0.005). On multivariate analysis, after adjusting for age, triglycerides and hypertension, the association of ε4 allele with stroke was found to be no longer statistically significant, OR (95%CI) 1.2 (0.4–4.5) (p = NS). On multiple logistic regression analysis age, OR (95%CI) 1.1 (1.1–1.2) (p < 0.001), and hypertension OR (95%CI) 15.1 (2.6–89.1) (p < 0.005) were found to be independent risk factors for development of stroke. This is the first report to have examined the association of apo E gene polymorphism with stroke in the Asian Indians. This study suggests that apo ε4 allele, triglycerides, age and hypertension are the predictors for stroke development. [ABSTRACT FROM AUTHOR]

Abstract: We evaluated the impact of three polymorphisms in the lipoprotein lipase gene (LPL) on coronary artery disease (CAD) susceptibility in Chinese and Asian Indian males residing in Singapore. A total of 1201 CAD patients and 841 healthy controls were recruited. The HindIII/H- and 447X alleles are associated with decreased CAD risk in both Chinese (p=0.025, 0.001, respectively) and Indians (p=0.0014, 0.008, respectively). The same effect of PvuII/P- allele was observed only in Indians (p=0.049). The most common haplotype, P+H+S, was significantly increased CAD risk in both ethnic groups (p=0.0096, 0.0011, respectively). [ABSTRACT FROM AUTHOR]