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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]

Abstract: Organophosphate (OP)-containing pesticides are widely used worldwide for domestic and industrial purposes. Studies on acute and chronic exposure to OPs have revealed numerous health effects attributed mainly to acetylcholinesterase (AChE) inhibition. The enzyme human serum paraoxonase (PON1) is involved in the detoxification of OP compounds. PON1 polymorphisms have been shown to affect susceptibility to OP exposure. We studied the effect of OP exposure on pest control workers and assessed the distribution of two common PON1 polymorphisms in our local population. The exposed group consisted of 103 workers from various pest control companies under the Singapore Pest Management Association while the 91 unexposed workers were from a lead stabilizer factory. For all workers, the mean age was 36.9 (20–70) years and the ethnic distribution was 38.1% Chinese, 44.3% Malay and 17.5% Indian. The mean±S.D. exposure duration among the pesticide workers was 10.4±8.4 years. The mean±S.D. RBC cholinesterase level was 18436.2±2078U/L and 18079.6±1576U/L for the exposed and unexposed groups, respectively (p =0.216). The mean±S.D. serum pseudocholinesterase was 11028.4±2867.4U/L and 9433.6±2022.6U/L in the exposed and unexposed groups, respectively (p <0.0001). Mean paraoxonase activity was similar among Chinese and Malays (266.5 and 266.3U/L, respectively) whereas that of the Indians was significantly lower (165.6U/L). Our study showed that cholinesterase levels among the exposed were not lower than those in the unexposed group. PON1 polymorphisms differed among ethnic groups, implying that ethnicity could be an important surrogate for identifying susceptible groups in case of OP exposure. Although OP poisoning is rare among occupationally exposed workers in Singapore, this information is useful for other developing countries that have large populations of Chinese, Malays and Indians where OP exposure could be very high especially in agricultural settings. [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]

Abstract: Introduction: Thrombospondin 1 and 2 are multidomain calcium-binding extracellular glycoproteins and they play a role in platelet aggregation, inflammatory response and assembly of connective tissue extracellular matrix. The association of thrombospondins (TSP) in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI) is well established. The association of the TSP-1 (Asn700Ser, 2210A→G, rs2228262) and TSP-2 un-translated region (UTR) (3949T→G, rs8089) gene variations among South Indian CAD and MI patients has been examined in the present study. Materials and Methods: We analyzed the thrombospondin polymorphisms in unrelated CAD patients (n=511) and a subgroup with an event of MI (n=173) compared with controls (n=522). The polymorphisms were assessed using polymerase chain reaction, restriction fragment length analysis and the circulating TSP concentration were measured using enzyme linked immune-sorbent assay. Results: The prevalence of TSP-1 and TSP-2 alleles did not show any significant difference statistically, when compared controls against CAD/MI patients. The rare GG genotype of the N700S polymorphism was not observed among the studied population. Further, multiple regression analysis revealed that there was no significant risk for CAD (OR=1.68; 95% CI 0.927 - 3.055; p=0.087) or MI (OR=1.84; 95% CI 0.846 - 4.007; p=0.124) for the GA genotype. The GA genotype showed no impact on clinical characteristics of the CAD patients and their circulating TSP-1 levels. A similar non-association was observed for the TSP-2 in 3949T→G polymorphism (GG genotype) for CAD (OR=0.64; 95% CI 0.278 - 1.455; p=0.636) and MI (OR=0.53; 95% CI 0.166 - 1.675; p=0.278). Conclusions: Our data suggests that the presence of thrombospondin-1 (rs2228262) and thrombospondin-2 (rs8089) variants need not be considered a risk for coronary artery disease or myocardial infarction among South Indians. [Copyright &y& Elsevier]