Totomoch-Serra Armando, Muñoz Maria de Lourdes, Burgueño Juan, Revilla-Monsalve Maria Cristina, Diaz-Badillo Alvaro
Centro de Investigación y de Estudios Avanzados del IPN, Mexico, Mexico.
Centro Internacional de Mejoramiento de Maíz y Trigo, Mexico, Mexico.
Arch Med Sci. 2018 Oct;14(6):1361-1373. doi: 10.5114/aoms.2018.74757. Epub 2018 Mar 28.
Genetic variants have been replicated for association with type 2 diabetes mellitus (T2D) and many of them with diabetes-related traits. Because T2D is highly prevalent in Mexico, this study aimed to test the association of , , , and gene polymorphisms (rs10811661, rs8192678, rs2010963, rs7896005 and rs659366 respectively) with metabolic traits in 415 unrelated Mexican mestizos with T2D under three models of inheritance.
A total of 415 unrelated Mexican mestizos were genotyped by TaqMan assays. Triglycerides, cholesterol, glucose, high-density lipoprotein cholesterol (HDL-C), insulin and anthropometric measurements were determined and the HOMA-IR was calculated. Association studies were tested by the Kruskal-Wallis test, linear regression, statistical power analysis, Bonferroni correction, paired SNP analysis, and physical interaction by GeneMANIA.
All polymorphisms were in Hardy-Weinberg equilibrium, and the association by genotype with T2D-related traits displayed nominal significance for rs8192678 with glucose ( = 0.023) and triglycerides ( = 0.013); rs2010963 with diastolic blood pressure (DBP) ( = 0.012) and cholesterol ( = 0.013); rs7896005 with DBP ( = 0.012) and insulin ( = 0.011); and rs659366 with cholesterol ( = 0.034), glucose ( = 0.031) and triglycerides ( = 0.028); and the association of rs2010963 with HDL-C ( = 0.0007) was significant. Linear regression performed with three models of inheritance, adjusted by age + sex + BMI and corrected with Bonferroni, showed a significant association of rs2010963 with HDL-C in an additive model ( = 0.007); and rs7896005 was significantly associated with DBP in the recessive model ( = 0.006).
Rigorous analysis evidenced the association of rs2010963 and rs7896005 with HDL-C and DBP respectively; these traits are known predictors of cardiovascular complications, which increase the risk of cardiovascular diseases in this population.
基因变异与2型糖尿病(T2D)的关联已得到重复验证,其中许多变异还与糖尿病相关性状有关。由于T2D在墨西哥非常普遍,本研究旨在在三种遗传模型下,检测415名无亲缘关系的患有T2D的墨西哥混血儿中, 、 、 、 和 基因多态性(分别为rs10811661、rs8192678、rs2010963、rs7896005和rs659366)与代谢性状的关联。
通过TaqMan检测法对415名无亲缘关系的墨西哥混血儿进行基因分型。测定甘油三酯、胆固醇、葡萄糖、高密度脂蛋白胆固醇(HDL-C)、胰岛素水平并进行人体测量,计算胰岛素抵抗指数(HOMA-IR)。通过Kruskal-Wallis检验、线性回归、统计功效分析、Bonferroni校正、配对单核苷酸多态性分析以及使用GeneMANIA进行物理相互作用分析来进行关联研究。
所有多态性均处于Hardy-Weinberg平衡状态,按基因型与T2D相关性状的关联分析显示,rs8192678与葡萄糖( = 0.023)和甘油三酯( = 0.013);rs2010963与舒张压(DBP)( = 0.012)和胆固醇( = 0.013);rs7896005与DBP( = 0.012)和胰岛素( = 0.011);rs659366与胆固醇( = 0.034)、葡萄糖( = 0.031)和甘油三酯( = 0.028)之间的关联具有名义显著性;rs2010963与HDL-C( = 0.0007)的关联显著。在年龄+性别+体重指数调整并经Bonferroni校正的三种遗传模型下进行线性回归分析,结果显示rs2010963在加性模型中与HDL-C存在显著关联( = 0.007);rs7896005在隐性模型中与DBP显著相关( = 0.006)。
严格分析证明rs2010963和rs7896005分别与HDL-C和DBP存在关联;这些性状是心血管并发症的已知预测指标,会增加该人群患心血管疾病的风险。