title: Association of calpain 10 gene polymorphisms with type 2 diabetes mellitus in Southern Indians.
abstract: The aim was to investigate the association between the CAPN10 gene single nucleotide polymorphisms (SNPs) -44 (rs2975760), -43 (rs3792267), -19 (rs3842570), and -63 (rs5030952) and type 2 diabetes mellitus in an Asian Indian population in Southern India. A total of 1443 subjects, 794 normal glucose tolerant (NGT) and 649 type 2 diabetes mellitus subjects, were randomly selected from the Chennai Urban Rural Epidemiology Study. These subjects were genotyped for the 4 CAPN10 SNPs using polymerase chain reaction-restriction fragment length polymorphism and validated by direct sequencing. None of the 4 SNPs showed any significant differences in the genotypic distribution among the NGT and type 2 diabetes mellitus subjects (P = .20, .86, .34, and .39 for SNPs -44, -43, -19, and -63, respectively). The NGT subjects with the 11 genotype of the SNP -63 had significantly higher 2-hour postload plasma glucose (mean ± SD, 5.66 ± 1.05 mmol/L) levels compared with the combined 12 and 22 genotype group (5.33 ± 1.11 mmol/L, P = .004). The P value remained significant even after adjusting for age, sex, body mass index, smoking, and alcohol consumption (nominal P = .008). No significant difference in the biochemical parameters was observed when the subjects were stratified according to the other SNPs. The 2111 haplotype corresponding to SNPs -44, -43, -19, and -63 showed a significant difference in the proportion among NGT (0.18) and type 2 diabetes mellitus subjects (0.22, nominal P = .014). Although the Bonferroni correction based on the asymptotic test does not preserve this significance, the test based on the empirical distribution remained significant. In conclusion, our study raises the possibility that the 2111 haplotype of SNPs -44, -43, -19, and -63 may be associated with type 2 diabetes mellitus, although none of these SNPs may be individually associated with diabetes.
authors.affiliation: Department of Molecular Genetics, Madras Diabetes Research Foundation-ICMR Advanced Centre for Genomics of Diabetes, Chennai 603 103, India.
authors.forename: Dhanasekaran
authors.initials: D
authors.lastname: Bodhini
authors.forename: Venkatesan
authors.initials: V
authors.lastname: Radha
authors.forename: Saurabh
authors.initials: S
authors.lastname: Ghosh
authors.forename: Krishna R
authors.initials: KR
authors.lastname: Sanapala
authors.forename: Partha P
authors.initials: PP
authors.lastname: Majumder
authors.forename: Manchanahalli Rangaswamy Satyanarayana
authors.initials: MR
authors.lastname: Rao
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Mohan
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000453:epidemiology; D001483:Base Sequence; D015992:Body Mass Index; D002154:Calpain / Q000235:genetics*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies / Q000706:statistics & numerical data*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000453:epidemiology; D014280:Triglycerides / Q000097:blood; D055105:Waist Circumference
chemical_list: D008078:Cholesterol, LDL; D014280:Triglycerides; D002784:Cholesterol; D002154:Calpain; C415197:calpain 10