Association analysis of common variants in FOXO3 with type 2 diabetes in a South Indian Dravidian population |
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| Authors: | Nair Anup Kumar Sugunan Divya Kumar Harish Anilkumar Gopalakrishnapillai |
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| Affiliation: | a Amrita School of Biotechnology, Amrita Vishwa Vidyapeetham, Amritapuri P.O., Kollam, Kerala, 690 525, Indiab Amrita Institute of Medical Science, Amrita Vishwa Vidyapeetham, AIMS Ponekkara P.O., Kochi, Kerala, 682 041, India |
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| Abstract: | Recent studies have identified common variants in forkhead box O3 gene (FOXO3) to be strongly associated with longevity in different populations. But studies have not been carried out to analyse the role of common variants in FOXO3 with type 2 diabetes. Since type 2 diabetes is an age related disorder and FOXO proteins play an important role in the regulation of metabolism, we studied the role of common variants in FOXO3 for association with type 2 diabetes. The study was carried out in 994 type 2 diabetic samples and 984 normoglycemic control samples from a South Indian Dravidian population. In our analysis, we found that there was no association between any of the selected SNPs in FOXO3 with type 2 diabetes. Analysis of these SNPs with diabetes related biochemical and clinical parameters also did not reveal any significant association. Haplotype association of SNPs in FOXO3 with type 2 diabetes was observed, but the frequency of the haplotypes was considerably lower and they do not remain significant after correction for multiple testing. In conclusion, we did not observe any association of SNPs in FOXO3 with type 2 diabetes and related parameters suggesting an entirely different mechanism by which these SNPs influence longevity. However additional studies in other populations are required to completely rule out the association of common variants in FOXO3 with type 2 diabetes. |
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| Keywords: | GLUT4, glucose transporter 4 PKB/AKT, protein kinase B PI3K, phosphatidylinositol 3 kinase FOXO, forkhead box group O IGFBP-1, insulin like growth factor binding protein-1 G6Pase, glucose 6 phosphatase PEPCK, phospho enol pyruvate carboxy kinase AMPK, AMP activated protein kinase SNP, Single nucleotide polymorphism LD, linkage disequilibrium MAF, minor allele frequency PCR, polymerase chain reaction ARMS PCR, amplification refractory mutation system PCR RFLP, restriction fragment length polymorphism BMI, body mass index HDL, high density lipoprotein LDL, low density lipoprotein |
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