Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, 143005, India.
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
Biochem Genet. 2021 Aug;59(4):966-996. doi: 10.1007/s10528-021-10041-2. Epub 2021 Feb 20.
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.
2 型糖尿病（T2D）及其继发性并发症是由遗传和环境因素的复杂相互作用引起的。为了了解这些因素对疾病易感性的作用，本研究评估了内皮型一氧化氮合酶（eNOS）和单核细胞趋化蛋白-1（MCP-1）变异与来自印度北部两个具有不同种族和地理特征的队列中的 T2D 和糖尿病肾病（DN）的相关性。对来自两个队列的 1313 名受试者进行了 eNOS（rs2070744、rs869109213 和 rs1799983）和 MCP-1（rs1024611 和 rs3917887）变异的基因分型。队列 I（旁遮普邦）包括 461 例 T2D 病例（204 例 T2D 合并 DN 和 257 例 T2D 不合并 DN）和 315 例健康对照。队列 II（查谟和克什米尔）包括 337 例 T2D（150 例 T2D 合并 DN 和 187 例 T2D 不合并 DN）和 200 例对照。比较了研究参与者中的等位基因、基因型和单倍型频率，并确定了表型-基因型相互作用。进行了荟萃分析以研究选定变体与疾病易感性之间的关联。在两个队列中，所有三个 eNOS 变体与 DN 的 1.5-4.0 倍风险相关。在队列 II 中，MCP-1 rs1024611 使 DN 进展的风险增加了两倍，而 rs3917887 在两个队列中均使 T2D 和 DN 的风险增加了两倍。eNOS 和 MCP-1 单倍型增加了 T2D 和 DN 易感性的风险。表型-基因型相互作用显示，研究的变体与人体测量学和生化参数之间存在显著关联。在荟萃分析中，所有 eNOS 变体均使 DN 进展的风险增加，而 MCP-1 rs1024611 则没有明显的关联。我们提供了内皮型一氧化氮合酶（eNOS）和单核细胞趋化蛋白-1（MCP-1）变体与 T2D 和 DN 易感性相关的证据。
