Interaction between the UCP2-866G/A, mtDNA 10398G/A and PGC1alpha p.Thr394Thr and p.Gly482Ser polymorphisms in type 2 diabetes susceptibility in North Indian population.
In the recent past, we have observed a possible role of 10398A and 16189C mtDNA and PGC1alpha p.Thr394Thr (rs2970847) and p.Gly482Ser (rs8192673) variant genotypes providing susceptibility/protection against type 2 diabetes mellitus (T2DM) in two North Indian population groups. These initial observations encouraged us to look at the candidate genes in combination with -866G/A (rs659366) polymorphism in uncoupling protein 2 (UCP2) in a single study of a relatively large sample size, constituted of both the cohorts, to unravel an interesting outcome of an additive interaction in-between the studied genes. In a total of 1,686 individuals (762 cases and 924 controls) belonging to Indo-European linguistic group from North India, a comparison of risk genotype combinations of: UCP2-866GG, mtDNA 10398A and PGC1alpha p.Thr394Thr or p.Gly482Ser against the protective genotypes: UCP2-866XA, mtDNA 10398G and PGC1alpha p.Thr394Thr (nominal P value = 1.75 x 10(-14), Odds ratio, OR = 5.29, 3.40-8.22 at 95% CI) or PGC1alpha p.Gly482Ser (nominal p value = 4.42 x 10(-24), OR = 8.59, 5.53-13.35 at 95% CI), showed a highly significant difference and increased ORs. In a complex disease, it is always encouraging to find an additive interaction of multiple small effects of the studied candidate gene variations.
Rai
E
E
National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067, India.
Sharma
S
S
Koul
A
A
Bhat
A K
AK
Bhanwer
A J S
AJ
Bamezai
R N K
RN
D000328:Adult; D000483:Alleles; D019943:Amino Acid Substitution; D016022:Case-Control Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006360:Heat-Shock Proteins / Q000235:genetics*; D006801:Humans; D007194:India; D007473:Ion Channels / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics*; D016017:Odds Ratio; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics*; D000071246:Uncoupling Protein 2
D004272:DNA, Mitochondrial; D006360:Heat-Shock Proteins; D007473:Ion Channels; D024101:Mitochondrial Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; C000604389:UCP2 protein, human; D000071246:Uncoupling Protein 2
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