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Approximately, 4-11 % of the patients with idiopathic venous thrombosis (VT) show protein C (PC) deficiency. The molecular pathology of PC deficiency was analyzed in 102 patients; 98 healthy controls were also studied to assess the association of various polymorphisms with reduced PC levels. PROC gene mutations were detected only in 8 (7.8 %) patients with reduced PC levels. PROC promoter region CG polymorphisms showed statistically significant association with reduced PC levels ( p < 0.001). PC deficiency in Indian VT patients can, thus, largely be explained by PROC gene promoter CG polymorphisms; only a small fraction of the patients show specific mutations in PROC gene. [ABSTRACT FROM AUTHOR]

Variants in genes involved in pancreatic β-cell development and function are known to cause monogenic forms of type 2 diabetes and are also associated with complex form. In this study, we studied the genetic association of polymorphisms in such important genes with type 2 diabetes in the high-risk Indians. We genotyped 91 polymorphisms in 19 genes (ABCC8, HNF1A, HNF1B, HNF4A, INS, INSM1, ISL1, KCNJ11, MAFA, MNX1, NEUROD1, NEUROG3, NKX2.2, NKX6.1, PAX4, PAX6, PDX1, USF1 and WFS1) in 2025 unrelated North Indians of Indo-European ethnicity comprising of 1019 diabetic and 1006 non-diabetic subjects. HNF4A promoter P2 polymorphisms rs1884613 and rs2144908, which are in high linkage disequilibrium, showed significant association with type 2 diabetes (odds ratio (OR)=1.37 (95% confidence interval (CI) 1.19-1.57), P=9.4 × 10−6 for rs1884613 and OR=1.37 (95%CI 1.20-1.57), P=6.0 × 10−6 for rs2144908), as previously shown in other populations. We observed body mass index-dependent association of these variants with type 2 diabetes in normal-weight/lean subjects. Variants in USF1, ABCC8, ISL1 and KCNJ11 showed nominal association, while haplotypes in these genes were significantly associated. rs3812704 upstream of NEUROG3 significantly increased risk for type 2 diabetes in normal-weight/lean subjects (OR=1.68 (95%CI 1.25-2.24), P=4.9 × 10−4). Thus, pancreatic β-cell development and function genes contribute to susceptibility to type 2 diabetes in North Indians. [ABSTRACT FROM AUTHOR]