The association of APLN polymorphisms with metabolic syndrome and the change of APLN gene expression treated with TNF-α

• Main Authors: Yi-Ning Li, 李依寧
• Other Authors: Suh-Hang Hank Juo
• Format: Others
• Language: zh-TW
• Published: 2009
• Online Access: http://ndltd.ncl.edu.tw/handle/48318419732955662663

碩士 === 高雄醫學大學 === 醫學遺傳學研究所 === 97 === Background and Purpose Dysregulation of the production of adipokines plays a pivotal role in the development of metabolic syndrome and cardiovascular comorbidity. Apelin , a newly identified adipokine, is novel up-regulated by insulin and obesity. The endogenous expression of Tumor necrosis factor-alpha (TNF-α) was reported a high correlation with apelin in adipocyte of human and rat. The purpose of present study is to investigate whether the polymorphisms at the gene encoding apelin confer risks for metabolic syndrome. The effect of TNF-α on expression of apelin will be also investigated. Methods The study subjects are volunteers who received health exam at the Kaohsiung Medical University Hospital. The diagnosis of metabolic syndrome is based on the modified version of National Cholesterol Education Program Adult Treatment Panel Ⅲ. We conducted a case-control association study using subjects with at least three of the five components of metabolic syndrome as cases and those with zero or one feature as controls. Four tagging SNPs at apelin gene were genotyped. We gathered clinical patients’ adipocyte primary cell culture. Isolated human adipose tissue-derived mesenchymal stem cells were induced to mature adipocyte then treated with TNF-α to measure apelin expression. Results A total of 498 cases and 1311 controls were included in the present study. Men were accounted for 51.4 % and the average age was 51.1 ?b 13.55 year-old. The four SNPs at the apelin gene were not statistically associated with metabolic syndrome. We further evaluated the apelin genetic effect on each of the five components of metabolic syndrome. SNP 3 appeared to be accounted for abdominal obesity (p = 0.023, adjusted age recessive model) and fasting glucose (p = 0.002, adjusted age dominant model). SNP 4 appeared to be accounted for abdominal obesity (p = 0.026, adjusted age dominant model). Apelin gene expression after 10 ng/ml TNF-α treated 1hour was significant different between sexual effect (p = 0.028). Conclusions The present study demonstrated that polymorphisms at the apelin gene may influence abdominal obesity and insulin resistance to the development of metabolic syndrome.