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-b1), 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-b1 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-b1 (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-b1 (rs1800470) may increase the risk of both ESRD and T2D in both populations, but TGF-b1 (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.

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Type 2 diabetes (T2D) and its secondary complications result from the complex interplay of genetic and environmental factors. To understand the role of these factors on disease susceptibility, the present study was conducted to assess the association of eNOS and MCP-1 variants with T2D and diabetic nephropathy (DN) in two ethnically and geographically different cohorts from North India. A total of 1313 subjects from two cohorts were genotyped for eNOS (rs2070744, rs869109213 and rs1799983) and MCP-1 (rs1024611 and rs3917887) variants. Cohort-I (Punjab) comprised 461 T2D cases (204 T2D with DN and 257 T2D without DN) and 315 healthy controls. Cohort-II (Jammu and Kashmir) included 337 T2D (150 T2D with DN and 187 T2D without DN) and 200 controls. Allele, genotype and haplotype frequencies were compared among the studied participants, and phenotype–genotype interactions were determined. Meta-analysis was performed to investigate the association between the selected variants and disease susceptibility. All three eNOS variants were associated with 1.5–4.0-fold risk of DN in both cohorts. MCP-1 rs1024611 conferred twofold risk towards DN progression in cohort-II, while rs3917887 provided twofold risk for both T2D and DN in both cohorts . eNOS and MCP-1 haplotypes conferred risk for T2D and DN susceptibility. Phenotype–genotype interactions showed significant associations between the studied variants and anthropometric and biochemical parameters. In meta-analysis, all eNOS variants conferred risk towards DN progression, whereas no significant association was observed for MCP-1 rs1024611. We show evidences for an association of eNOS and MCP-1 variants with T2D and DN susceptibility. Supplementary Information The online version contains supplementary material available at 10.1007/s10528-021-10041-2.

A middle aged chronic alcoholic presented with deep jaundice, markedly enlarged and tender spleen with leukoerythroblastic blood picture and bone marrow biopsy showing mild fibrosis. He was tested negative for HIV, hepatitis B and C viruses. Besides very high serum bilirubin, alkaline phosphatase was raised four times the normal value. Contrast enhanced CT showed enlarged spleen and liver with multiple heterogenous lesions in spleen and tiny hypo-dense lesions in liver. In hospital, he developed haemolytic uraemic syndrome and succumed to his illness. At autopsy spleen weighed 5200 gms and variegated in appearance due to large areas of necrosis and whitish tumour nodules. Histology revealed morphology of an angiosarcoma. Liver was also infiltrated by the tumour mainly in and around portal tract areas.

Diabetic nephropathy (DN) is a major cause of renal failure globally including chronic kidney disease and end-stage renal disease (ESRD). Using comprehensive linkage disequilibrium mapping, we genotyped five polymorphisms from engulfment and cell motility 1 (ELMO1) gene (rs741301, rs7799004, rs1882080, rs11769038 and rs1345365) to evaluate its association with DN. BMI was observed to be low in DN cases as compared to the control groups, which is the result of haemodialysis and high doses of medication. Physical inactivity, lipid profile, urea and creatinine were observed to be the confounding factors correlated with DN. This study comprehensively evaluated ELMO1 in DN patients, T2D without Nephropathy and healthy controls from North Indian population and revealed significant association with DN. Haplotypes G-G-C-C and G-A-T-T provided ~2-fold risk towards DN development. In conclusion, the present study suggests the significant role of ELMO1 gene polymorphisms in the pathophysiology of DN in North-Indian population.