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Abstract：
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.
摘要：
2型糖尿病（T2D）及其继发性并发症是遗传和环境因素复杂相互作用的结果。为了了解这些因素对疾病易感性的作用，本研究旨在评估来自北印度的两个种族和地理不同的队列中eNOS和MCP-1变异与T2D和糖尿病肾病(DN)的相关性.对来自两个队列的总共1313名受试者进行了eNOS(rs2070744、rs869109213和rs1799983)和MCP-1(rs1024611和rs3917887)变体的基因分型。队列I（旁遮普）包括461例T2D病例（204例T2D伴DN，257例T2D不伴DN）和315例健康对照。队列II（查谟和克什米尔）包括337个T2D（150个有DN的T2D和187个无DN的T2D）和200个对照。等位基因,基因型和单倍型频率在研究参与者之间进行了比较，并确定了表型-基因型的相互作用。进行荟萃分析以研究所选变异与疾病易感性之间的关联。在两个队列中，所有三种eNOS变体均与DN的1.5-4.0倍风险相关。MCP-1rs1024611在队列II中赋予DN进展的两倍风险，而rs3917887在两个队列中提供了T2D和DN的两倍风险。eNOS和MCP-1单倍型赋予了T2D和DN易感性的风险。表型-基因型相互作用显示所研究的变体与人体测量和生化参数之间存在显着关联。在荟萃分析中，所有eNOS变体都赋予DN进展的风险，而MCP-1rs1024611未观察到显著关联。我们显示了eNOS和MCP-1变体与T2D和DN易感性相关的证据。
