title: Replication of type 2 diabetes candidate genes variations in three geographically unrelated Indian population groups.
abstract: Type 2 diabetes (T2D) is a syndrome of multiple metabolic disorders and is genetically heterogeneous. India comprises one of the largest global populations with highest number of reported type 2 diabetes cases. However, limited information about T2D associated loci is available for Indian populations. It is, therefore, pertinent to evaluate the previously associated candidates as well as identify novel genetic variations in Indian populations to understand the extent of genetic heterogeneity. We chose to do a cost effective high-throughput mass-array genotyping and studied the candidate gene variations associated with T2D in literature. In this case-control candidate genes association study, 91 SNPs from 55 candidate genes have been analyzed in three geographically independent population groups from India. We report the genetic variants in five candidate genes: TCF7L2, HHEX, ENPP1, IDE and FTO, are significantly associated (after Bonferroni correction, p<5.5E-04) with T2D susceptibility in combined population. Interestingly, SNP rs7903146 of the TCF7L2 gene passed the genome wide significance threshold (combined P value = 2.05E-08) in the studied populations. We also observed the association of rs7903146 with blood glucose (fasting and postprandial) levels, supporting the role of TCF7L2 gene in blood glucose homeostasis. Further, we noted that the moderate risk provided by the independently associated loci in combined population with Odds Ratio (OR)<1.38 increased to OR = 2.44, (95%CI = 1.67-3.59) when the risk providing genotypes of TCF7L2, HHEX, ENPP1 and FTO genes were combined, suggesting the importance of gene-gene interactions evaluation in complex disorders like T2D.
authors.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors.forename: Shafat
authors.initials: S
authors.lastname: Ali
authors.forename: Rupali
authors.initials: R
authors.lastname: Chopra
authors.forename: Siddharth
authors.initials: S
authors.lastname: Manvati
authors.forename: Yoginder Pal
authors.initials: YP
authors.lastname: Singh
authors.forename: Nabodita
authors.initials: N
authors.lastname: Kaul
authors.forename: Anita
authors.initials: A
authors.lastname: Behura
authors.forename: Ankit
authors.initials: A
authors.lastname: Mahajan
authors.forename: Prabodh
authors.initials: P
authors.lastname: Sehajpal
authors.forename: Subash
authors.initials: S
authors.lastname: Gupta
authors.forename: Manoj K
authors.initials: MK
authors.lastname: Dhar
authors.forename: Gagan B N
authors.initials: GB
authors.lastname: Chainy
authors.forename: Amarjit S
authors.initials: AS
authors.lastname: Bhanwer
authors.forename: Swarkar
authors.initials: S
authors.lastname: Sharma
authors.forename: Rameshwar N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000483:Alleles; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D062306:Geography, Medical; D006801:Humans; D007194:India / Q000453:epidemiology; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide