Association of genetic variants in INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) with type 2 diabetes (T2D): a case-control study in three ethnic groups from North-West India.

Genetic contributions towards Type 2 diabetes (T2D) have been assessed through association studies across different world populations with inconsistencies. The majority of the T2D susceptibility loci are common across different races or populations but show ethnicity-specific differences. The pathogenesis of T2D involves genetic variants in the candidate genes. The interactions between the genes involved in insulin signaling and secretory pathways are believed to play an important role in determining an individual's susceptibility towards T2D. Therefore, the present study was initiated to examine the differences, if any, in the contribution of polymorphisms towards T2D susceptibility in the background of different ethnic specifications. The present case-control study included a total of 1216 T2D cases and healthy controls from three ethnic groups (Jat Sikhs, Banias and Brahmins) of North-West India. Polymorphisms were selected on the basis of information available in the literature for INS (rs689), INSR (rs1799816) and PP1G.G (rs1799999) in context to T2D. The genotyping was done using PCR-RFLP method. Statistical analysis was done using SPSS 16.0. The analyses revealed that INS (rs689) polymorphism conferred risk towards T2D susceptibility in all the three ethnic groups whereas INSR (rs1799816) polymorphism conferred risk towards T2D in Brahmins only and PP1G.G (rs1799999) polymorphism indicated T2D risk in Jat Sikhs only. Furthermore, interaction analyses indicated the cumulative role of three genetic variants in modulating T2D susceptibility in the three ethnic groups. In conclusion, our results substantiated the evidences for the role of ethnicity in differential susceptibility to T2D in the background of same genetic variants.

Associating genetic variation at Perilipin 1, Complement Factor D and Adiponectin loci to the bone health status in North Indian population.

Osteoporosis, the most common bone metabolic disease affecting nearly 200 million people worldwide is under the strong influence of genetic components. Simultaneously, adipogenesis and osteogenesis are two highly coordinated processes imperative for the maintenance of bone quality and quantity, where any perturbation leads to pathological conditions of obesity, osteopenia and osteoporosis. To delineate this adipogenic-osteogenic connection, a total of 254 cases (T-score<-1.0 SD) and 250 age, gender and ethnicity matched healthy controls (T-score≥-1.0 SD) were recruited from North India after analyzing bone health status employing quantitative ultrasound (QUS) bone densitometer. The genetic variants of Perilipin 1 (PLIN1), Complement Factor D (CFD) and Adiponectin (ADIPOQ) were genotyped using the PCR-RFLP/ARMS-PCR approach. Subjects with CC+CT (PLIN1 rs2304795) and CC+CG (CFD rs1683563) genotypes conferred nearly 1.54-1.87 fold increased risk towards bone deterioration. Predicted RNA secondary structures of rs2304795 corroborated the risk associated with wild type C allele. G allele carriers at the ADIPOQ locus (rs1501299) were more likely to have a lower bone health (1.57-fold). Haplotype analysis revealed the ADIPOQ variants rs1501299 and rs3774261 in slight linkage disequilibrium (LD), nonetheless G/G haplotype was associated with increased risk. 3-locus and 5-locus gene-gene interaction models revealed a greater likelihood of bone deterioration. In conclusion, certain variants of adipogenic genes might serve as potential biomarkers for determining the genetic predisposition towards bone loss in the North Indian population, further, emphasizing the role of impaired metabolism in bone health.

Association of Transforming Growth Factor Beta-1 (TGF-ß1) Genetic Variation with Type 2 Diabetes and End Stage Renal Disease in Two Large Population Samples from North India.

Geographic and ethnic differences impart an immense influence on the genetic susceptibility to Type 2 diabetes (T2D) and diabetic nephropathy (DN). Transforming growth factor-beta1 (TGF-ß1), a ubiquitously expressed pro-fibrotic cytokine plays a pivotal role in mediating the hypertrophic and fibrotic manifestations of DN. The present study is aimed to study the association of TGF-ß1 g.869T>C (rs1800470) and g.-509C>T (rs1800469) polymorphism in T2D and end stage renal disease (ESRD) cases from the two geographically and ethnically different populations from North India. A total of 1313 samples comprising 776 samples from Punjab (204 with ESRD, 257 without ESRD, and 315 healthy controls) and 537 samples from Jammu and Kashmir (150 with ESRD, 187 without ESRD, and 200 controls) were genotyped for TGF-ß1 (rs1800470 and rs1800469) using ARMS-PCR. The CC genotype of rs1800470 increased ESRD risk by 3.1-4.5-fold in both populations. However, for rs1800469, the TT genotype provided 5.5-fold risk towards ESRD cases from Jammu and Kashmir and no risk for the cases from Punjab. The haplotype C-T conferred nearly a 2-3-fold risk towards T2D and ESRD and diplotype CC-CT conferred a 4-fold risk towards ESRD. Our results conclude that TGF-ß1 (rs1800470) may increase the risk of both ESRD and T2D in both populations, but TGF-ß1 (rs1800469) provided risk for only ESRD in the population of Jammu and Kashmir. The present study is one of the large sample sized genetic association studies of T2D and ESRD from Indian population and adds to the scholarship on global health omics.