线粒体基因组控制区变异与一组墨西哥混血儿2型糖尿病的关联
Variants in the Control Region of Mitochondrial Genome Associated with type 2 Diabetes in a Cohort of Mexican Mestizos.
作者信息
Santander-Lucio Heriberto, Totomoch-Serra Armando, Muñoz María de Lourdes, García-Hernández Normand, Pérez-Ramírez Gerardo, Valladares-Salgado Adán, Pérez-Muñoz Ashael Alfredo
机构信息
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México.
Departamento de Genética y Biología Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México, México; Departamento de Electrofisiología, Instituto Nacional de Cardiología, Ignacio Chávez, Ciudad de México, México.
出版信息
Arch Med Res. 2023 Feb;54(2):113-123. doi: 10.1016/j.arcmed.2022.12.014. Epub 2023 Feb 13.
BACKGROUND
According to the International Diabetes Federation, Mexico is seventh place in the prevalence of type 2 diabetes (T2D) worldwide. Mitochondrial DNA variant association studies in multifactorial diseases like T2D are scarce in Mexican populations.
AIM OF THE STUDY
The objective of this study was to analyze the association between 18 variants in the mtDNA control region and T2D and related metabolic traits in a Mexican mestizo population from Mexico City.
METHODS
This study included 1001 participants divided into 477 cases with T2D and 524 healthy controls aged between 42 and 62 years and 18 mtDNA variants with frequencies >15%.
RESULTS
Association analyses matched by age and sex showed differences in the distribution between cases and controls for variants m.315_316insC (p = 1.18 × 10), m.489T>C (p = 0.009), m.16362T>C (p = 0.001), and m.16519T>C (p = 0.004). The associations between T2D and variants m.315_316ins (OR = 6.13, CI = 3.42-10.97, p = 1.97 × 10), m.489T>C (OR = 1.45, CI = 1.00-2.11, p = 0.006), m.16362T>C (OR = 2.17, CI = 1.57-3.00, p = 0.001), and m.16519T>C (OR = 1.69, CI = 1.23-2.33, p = 0.006) were significant after performing logistic regression models adjusted for age, sex, and diastolic blood pressure. Metabolic traits in the control group through linear regressions, adjusted for age, sex and BMI, and corrected for multiple comparisons showed nominal association between glucose and variants m.263A>G (p <0.050), m.16183A>C (p <0.010), m.16189T>C (p <0.020), and m.16223C>T (p <0.024); triglycerides, and cholesterol and variant m.309_310insC (p <0.010 and p <0.050 respectively); urea, and creatinine, and variant m.315_316insC (p <0.007, and p <0.004 respectively); diastolic blood pressure and variants m.235A>G (p <0.016), m.263A>G (p <0.013), m.315_316insC (p <0.043), and m.16111C>T (p <0.022).
CONCLUSION
These results demonstrate a strong association between variant m.315_316insC and T2D and a nominal association with T2D traits.
背景
根据国际糖尿病联盟的数据，墨西哥在全球2型糖尿病（T2D）患病率方面位居第七。在墨西哥人群中，针对T2D等多因素疾病进行的线粒体DNA变异关联研究较少。
研究目的
本研究的目的是分析墨西哥城墨西哥混血人群中线粒体DNA控制区的18种变异与T2D及相关代谢特征之间的关联。
方法
本研究纳入了1001名参与者，分为477例T2D患者和524名年龄在42至62岁之间的健康对照，以及18种频率>15%的线粒体DNA变异。
结果
按年龄和性别匹配的关联分析显示，变异m.315_316insC（p = 1.18×10）、m.489T>C（p = 0.009）、m.16362T>C（p = 0.001）和m.16519T>C（p = 0.004）在病例组和对照组之间的分布存在差异。在对年龄、性别和舒张压进行调整的逻辑回归模型分析后，T2D与变异m.315_316ins（OR = 6.13，CI = 3.42 - 10.97，p = 1.97×10）、m.489T>C（OR = 1.45，CI = 1.00 - 2.11，p = 0.006）、m.16362T>C（OR = 2.17，CI = 1.57 - 3.00，p = 0.001）和m.16519T>C（OR = 1.69，CI = 1.23 - 2.33，p = 0.006）之间的关联具有统计学意义。通过对年龄、性别和BMI进行调整，并对多重比较进行校正的线性回归分析，对照组中的代谢特征显示，葡萄糖与变异m.263A>G（p < 0.050）、m.16183A>C（p < 0.010）、m.16189T>C（p < 0.020）和m.16223C>T（p < 0.024）之间存在名义上的关联；甘油三酯、胆固醇与变异m.309_310insC（分别为p < 0.010和p < 0.050）之间存在关联；尿素、肌酐与变异m.315_316insC（分别为p < 0.007和p < 0.004）之间存在关联；舒张压与变异m.235A>G（p < 0.016）、m.263A>G（p < 0.013）、m.315_316insC（p < 0.043）和m.16111C>T（p < 0.022）之间存在关联。
结论
这些结果表明变异m.315_316insC与T2D之间存在强关联，与T2D相关特征存在名义上的关联。
Zotero 插件