RESUMEN

BACKGROUND & OBJECTIVES: The genome-wide association studies (GWAS) have shown an association of type 2 diabetes mellitus (T2DM) with several novel genes. We report here the findings on the pattern of genetic association of three genes (CDKAL1, CDKN2A/B and HHEX) with T2DM in the population of Hyderabad, south India. METHODS: A sample of 1379 individuals (758 T2DM cases and 621 controls) from Hyderabad, India, were genotyped for five single nucleotide polymorphisms (SNPs) of CDKAL1 (rs7754840, rs7756992) CDKN2A/B (rs10811661) and HHEX (rs1111875, rs7923837) genes on Sequenom Mass Array platform. RESULTS: The risk allele frequencies of the CDKAL1 and CDKN2A/B SNPs were relatively higher in cases than in the controls and the logistic regression analysis yielded significant odds ratios suggesting that the variant alleles conferred risk for developing T2DM in this population. the HHEX gene did not show either allelic or genotypic association with T2DM. The multivariate logistic regression analysis with reference to both alleles and genotypes of CDKAL1 SNPs showed significant association, suggesting an important role for this gene in the T2DM pathophysiology. INTERPRETATION & CONCLUSIONS: A significant association was seen of all the three SNPs of CDKAL1 and CDKN2A/B genes with T2DM but none of the two SNPs of HHEX. Further studies are required to cross-validate our findings in a relatively larger sample. It is also necessary to explore other SNPs of HHEX gene to unequivocally establish the pattern of association of this gene with T2DM in this population.

Asunto(s)

Inhibidor p18 de las Quinasas Dependientes de la Ciclina/genética , Diabetes Mellitus Tipo 2/genética , Proteínas de Homeodominio/genética , Factores de Transcripción/genética , ARNt Metiltransferasas/genética , Adulto , Anciano , Anciano de 80 o más Años , Inhibidor p16 de la Quinasa Dependiente de Ciclina , Diabetes Mellitus Tipo 2/patología , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Estudio de Asociación del Genoma Completo , Genotipo , Humanos , India , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple

RESUMEN

Genome-wide association studies identified novel genes associated with T2DM which have been replicated in different populations. We try to examine here if certain frequently replicated SNPs of Insulin growth factor 2 m-RNA binding protein 2 (IGF2BP2) (rs4402960, rs1470579) and Solute Carrier family 30 member 8 (SLC30A8) (rs13266634) genes, known to be implicated in insulin pathway, are associated with T2DM in the population of Hyderabad, which is considered to be a diabetic capital of India. Genotyping of the 1379 samples, 758 cases and 621 controls, for the SNPs was performed on sequenom massarray platform. The logistic regression analysis was done using SPSS software and the post-hoc power of the study was estimated using G power. The allele and genotype frequencies were similar between cases and controls, both for SNPs of IGF2BP2 and SLC30A8 genes. Logistic regression did not reveal significant allelic or genotypic association of any of the three SNPs with T2DM. Despite large sample size and adequate power, we could not replicate the association of IGF2BP2 and SLC30A8 SNPs with T2DM in our sample from Hyderabad (A.P.), India, albeit another study based on much larger sample but from heterogeneous populations from the northern parts of India showed significant association of two of the above 3 SNPs, suggesting variable nature of susceptibility of these genes in different ethnic groups. Although the IGF2BP2 and SLC30A8 genes are important in the functional pathway of Insulin secretion, it appears that these genes do not play a significant role in the susceptibility to T2DM in this population.