RESUMEN
BACKGROUND & OBJECTIVES: Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder of premenopausal women. Given the phenotypic overlap between PCOS and type 2 diabetes mellitus (T2DM), this study was carried out to investigate whether genes implicated in T2DM were also involved in the susceptibility to PCOS among women from southern India. METHODS: A total of 248 women with PCOS and 210 healthy women as controls were genotyped for a panel of 15 single nucleotide polymorphisms (SNPs) from the nine T2DM genes, such as TCF7L2, IGF2BP2, SLC30A8, HHEX, CDKAL1, CDKN2A, IRS1, CAPN10 and PPARG, on Sequenom MassARRAY platform. RESULTS: None of the 15 SNPs were found to be significantly associated with PCOS after Bonferroni correction for multiple testing, either in the univariate or multivariate context. The cumulative effect of risk alleles observed with reference to T2DM was also not seen with reference to PCOS. INTERPRETATION & CONCLUSIONS: The nine T2DM genes considered in this exploratory study might not be the primary susceptibility factors for PCOS among Indian women. Our results supplement the lack of evidence of the association of T2DM genes with PCOS among the Chinese and Caucasians hinting at the possible universality of this pattern. Specifically designed comprehensive studies that include women with T2DM and PCOS are required to explore the precise role of the diabetes genes.
Asunto(s)
Diabetes Mellitus Tipo 2/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Síndrome del Ovario Poliquístico/genética , Alelos , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/patología , Femenino , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , India , Síndrome del Ovario Poliquístico/etiología , Síndrome del Ovario Poliquístico/patología , Polimorfismo de Nucleótido SimpleRESUMEN
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 SimpleRESUMEN
BACKGROUND: We attempted to validate earlier findings on the nature of the association of the IRS1, CAPN10, and PPARG genes with type 2 diabetes mellitus (T2DM) in the high-risk population of Hyderabad, India. METHODS: A sample of 1379 subjects (758 T2DM patients, 621 controls) was genotyped for single nucleotide polymorphisms (SNPs) of the IRS1 (rs1801278), CAPN10 (rs3792267, rs5030952), and PPARG (rs1801282) genes. RESULTS: The allele and genotype frequencies of IRS1 (rs1801278) and CAPN10 (rs3792267) SNPs differed significantly between the patient and control groups. Logistic regression analysis suggested a significant association of these two SNPs (P ≤ 0.007) with T2DM and the strength of association did not alter when adjusted for age, gender, body mass index, and the waist : hip ratio as covariates. The same two SNPs showed significant association in multivariate logistic regression analyses, even after Bonferroni correction for multiple testing, suggesting an independent nature of the role of these genes in the manifestation of T2DM in our population. CONCLUSIONS: We replicated the significant association of rs1801278 and rs3792267 SNPs of the IRS1 and CAPN10 genes with T2DM in the population of Hyderabad. Despite the known biological significance of the PPARG gene and a sufficient statistical power of the present study, we could not replicate the association of PPARG with T2DM in our high-risk population. Given the vast ethnic, geographic, and genetic heterogeneity of the Indian population, many more studies are needed covering the ethnic and geographic heterogeneity of India to enable identification of an Indian-specific profile of genes associated with T2DM.
Asunto(s)
Calpaína/genética , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad , Proteínas Sustrato del Receptor de Insulina/genética , PPAR gamma/genética , Polimorfismo de Nucleótido Simple , Alelos , Índice de Masa Corporal , Frecuencia de los Genes , Genotipo , Haplotipos , Humanos , IndiaRESUMEN
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.