School of Public Health, Guangdong Medical University, Dongguan 523808, China.
Biomed Res Int. 2021 Sep 20;2021:5517364. doi: 10.1155/2021/5517364. eCollection 2021.
This study is aimed at analyzing the relationship between leptin (LEP) signaling pathway and type 2 diabetes mellitus (T2DM) and at providing support for molecular genetic research on the pathogenesis of T2DM in Chinese Han population.
A case-control study was designed, including 1092 cases with T2DM and 1092 healthy controls of Chinese Han origin recruited from ten hospitals in Guangdong Province, Southern China. Twenty-three single nucleotide polymorphisms (SNPs) of 15 genes in LEP signaling pathway were genotyped by SNPscan™ kit. The Pearson chi-square test, Cochran-Armitage trend test, MAX3, and logistic regression were applied to analyze the association between single nucleotide polymorphism (SNP) and T2DM; unconditional logistic regression was used to analyze haplotype in LD block; and SNP set analysis based on logistic kernel machine regression was used to analyze pathway. All statistical analysis was performed by SPSS25.0, R2.14, Haploview4.2, SNPStats, and other statistical software packages.
In association analysis based on SNP, rs2167270 had statistical significance both in the adjusted and unadjusted covariate dominant model and in the unadjusted covariate overdominant model while it had no significant difference in the adjusted covariate overdominant model. Compared to GG genotype, rs2167270 of AG genotype had statistical significance in both the adjusted and unadjusted covariate codominant models. And rs16147 had statistical significance in robust test, stealth model and overdominant model, and adjusting and unadjusting covariate. This study found linkage disequilibrium existed between rs2167270 and rs4731426 of LEP, rs10889502 and rs17127107 of JAK1, rs2970847 and rs6821591 of PPARGC1A, rs249429 and rs3805486 of PRKAA1, rs1342382 and rs6588640 of PRKAA2, rs3766522 and rs6937 of PRKAB2, rs2970847 and rs6821591 of PRKAG2, and rs6436094 and rs645163 of PRKAG3. There was no positive finding with statistical significance from the unconditional logistic regression of the mentioned genes' haplotype of LD block.
LEP signaling pathway association with T2DM remained to be confirmed in Chinese Han population, although rs2167270 and rs16147 were significantly associated with T2DM.
本研究旨在分析瘦素（LEP）信号通路与 2 型糖尿病（T2DM）之间的关系，并为中国汉族人群 T2DM 发病机制的分子遗传研究提供支持。
采用病例对照研究设计，纳入 1092 例 T2DM 患者和 1092 例来自中国南方广东省 10 家医院的健康对照者。采用 SNPscan™试剂盒对 LEP 信号通路中的 15 个基因的 23 个单核苷酸多态性（SNP）进行基因分型。采用 Pearson 卡方检验、Cochran-Armitage 趋势检验、MAX3 和 logistic 回归分析 SNP 与 T2DM 的关联；采用无条件 logistic 回归分析连锁不平衡块中的单体型；采用基于 logistic 核机器回归的 SNP 集分析分析途径。所有统计分析均采用 SPSS25.0、R2.14、Haploview4.2、SNPStats 和其他统计软件包进行。
在基于 SNP 的关联分析中，rs2167270 在调整和未调整协变量显性模型以及未调整协变量超显性模型中均具有统计学意义，而在调整协变量超显性模型中则无显著差异。与 GG 基因型相比，AG 基因型的 rs2167270 在调整和未调整协变量共显性模型中均具有统计学意义。rs16147 在稳健性检验、隐匿模型和超显性模型以及调整和未调整协变量中均具有统计学意义。本研究发现 LEP 的 rs2167270 与 rs4731426、JAK1 的 rs10889502 和 rs17127107、PPARGC1A 的 rs2970847 和 rs6821591、PRKAA1 的 rs249429 和 rs3805486、PRKAA2 的 rs1342382 和 rs6588640、PRKAB2 的 rs3766522 和 rs6937、PRKAG2 的 rs2970847 和 rs6821591 以及 PRKAG3 的 rs6436094 和 rs645163 之间存在连锁不平衡。LD 块中所述基因单体型的无条件 logistic 回归未发现具有统计学意义的阳性结果。
尽管 rs2167270 和 rs16147 与 T2DM 显著相关，但 LEP 信号通路与 T2DM 的关联仍需在中国汉族人群中进一步证实。
