ABSTRACT
ANTECEDENTES: La nefropatía diabética (ND) es una complicación importante de la diabetes mellitus de tipo 2 (DMT2) con altas tasas de morbilidad mundial. OBJETIVO: Determinar la asociación del polimorfismo rs1801282 de PPAR en la DMT2 y la ND en la población del sur de India. MÉTODOS: Hemos llevado a cabo un estudio de casos y controles para analizar la asociación del polimorfismo rs1801282 con la DMT2 y la ND en 424 sujetos (ND = 128; DMT2 = 148 y controles = 148) pertenecientes a la población del sur de India mediante RCP-ARMS y método de secuenciación de Sanger. Además, se realizó un metaanálisis para el polimorfismo de rs1801282 a partir de la literatura publicada en varias bases de datos electrónicas para determinar la sensibilidad entre la DMT2 y la ND en varias poblaciones étnicas con 5 modelos genéticos. RESULTADOS: El genotipado de polimorfismo rs1801282 demostró una asociación significativa (valor de p < 0,05) con la ND y la DMT2 en comparación con los controles. En el metaanálisis no se observó asociación significativa (valor de p > 0,05) de rs1801282 con la ND frente a los controles en modelos genéticos homocigóticos, heterocigóticos, alélicos, recesivos y dominantes. Sin embargo, se observó una asociación significativa entre el polimorfismo de nucleótido único (PNU) rs1801282 SNP y la DMT2 en el modelo genético heterocigótico (Jj frente a JJ) con OR = 0,56, (IC del 95%: 0,43-0,74; p ≤ 0,0001 de poblaciones asiáticas y caucásicas. CONCLUSIÓN: El análisis general sugiere que el polimorfismo rs1801282 puede asociarse a ND y a DMT2. Se precisan más estudios de casos y controles sobre el gen PPAR con un taman o de la muestra mayor que incluya todos los factores de confusión para corroborar los resultados de este metaanálisis
BACKGROUND: Diabetic Nephropathy (DN) is a major complication of Type 2 Diabetes Mellitus (T2DM) with high morbidity rates worldwide. OBJECTIVE: To determine the association of PPAR rs1801282 polymorphism in T2DM and DN in south Indian population. METHODS: We have conducted a case-control study to test the association of rs1801282 polymorphism with T2DM and DN in 424 subjects (DN = 128; T2DM = 148 and controls = 148) belonging to the south Indian population using ARMS-PCR and Sanger sequencing method. Further, a meta-analysis was performed for rs1801282 polymorphism from the published literature retrieved from various electronic databases to determine the susceptibility among T2DM and DN across various ethnic populations under five genetic models. RESULTS: The genotyping of rs1801282 polymorphism showed significant (p-value < 0.05) association with DN and T2DM compared to controls. In the meta-analysis, no significant association (p-value > 0.05) was noticed for rs1801282 with DN vs. controls in homozygote, heterozygote, allelic, recessive and dominant genetic models. However, a significant association was observed between rs1801282 SNP and T2DM under heterozygote (Jj vs JJ) genetic model with OR = 0.56, (95%CI [0.43-0.74]), p ≤ 0.0001 of Asian and Caucasian populations. CONCLUSION: Overall analysis suggests that the rs1801282 polymorphism might be associated with DN and T2DM. More case-control studies on the PPAR gene with a larger sample size including all the confounding factors are required to corroborate the findings from this meta-analysis
Subject(s)
Humans , Middle Aged , Aged , Diabetes Mellitus, Type 2/genetics , Diabetic Nephropathies/genetics , PPAR gamma/genetics , Polymorphism, Single Nucleotide , Case-Control Studies , Confounding Factors, Epidemiologic , Racial Groups/genetics , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/ethnology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/ethnology , Ethnicity/genetics , Gene Frequency , Genetic Predisposition to Disease , Genotype , India/epidemiology , Models, Genetic , Sample SizeABSTRACT
Type-2 Diabetes mellitus (T2DM) is a complex metabolic disease. A case-control study was conducted with 218 T2DM and 214 controls to evaluate the T2DM risk of rs5219 polymorphism in the south Indian population. The analysis of allelic and genotype data showed a significant association of rs5219 polymorphism towards an increased risk of T2DM compared to controls with an odds ratio (OR) of 2.52, confidence interval (CI) (0.96-6.64) and p-value 0.046. The functional influence of rs5219 was tested which showed a significant correlation with HbA1c and serum uric acid levels. Although our results confirm rs5219 is a potential contributor to T2DM, several inconclusive results were noticed across the literature. Hence, the meta-analysis was performed by combining the results of case-control study with previous literature to confirm the rs5219 association with T2DM across various populations. Our meta-analysis revealed a significant risk association of rs5219 in T2DM under five genetic models. In summary, our analysis suggests, rs5219 polymorphism plays a significant role in T2DM susceptibility. Further, studies need to be conducted to determine the influence of rs5219 on the other characteristics of T2DM.
