在欧美不同年龄段成年人的社区样本中，即青年动脉粥样硬化风险发展研究和心血管健康研究中，HNF1A基因的常见编码变异与多种心血管风险表型相关。
Common coding variants of the HNF1A gene are associated with multiple cardiovascular risk phenotypes in community-based samples of younger and older European-American adults: the Coronary Artery Risk Development in Young Adults Study and The Cardiovascular Health Study.
作者信息
Reiner Alexander P, Gross Myron D, Carlson Christopher S, Bielinski Suzette J, Lange Leslie A, Fornage Myriam, Jenny Nancy S, Walston Jeremy, Tracy Russell P, Williams O Dale, Jacobs David R, Nickerson Deborah A
机构信息
Department of Epidemiology, University of Washington, Seattle, WA 98195, USA.
出版信息
Circ Cardiovasc Genet. 2009 Jun;2(3):244-54. doi: 10.1161/CIRCGENETICS.108.839506. Epub 2009 Apr 6.
BACKGROUND
The transcription factor hepatocyte nuclear factor (HNF)-1 alpha regulates the activity of a number of genes involved in innate immunity, blood coagulation, lipid and glucose transport and metabolism, and cellular detoxification. Common polymorphisms of the HNF-1 alpha gene (HNF1A) were recently associated with plasma C-reactive protein and gamma-glutamyl transferase concentration in middle-aged to older European Americans (EA).
METHODS AND RESULTS
We assessed whether common variants of HNF1A are associated with C-reactive protein, gamma-glutamyl transferase, and other atherosclerotic and metabolic risk factors, in the large, population-based Coronary Artery Risk Development in Young Adults Study of healthy young EA (n=2154) and African American (AA; n=2083) adults. The minor alleles of Ile27Leu (rs1169288) and Ser486Asn (rs2464196) were associated with 0.10 to 0.15 standard deviation units lower C-reactive protein and gamma-glutamyl transferase levels in EA. The same HNF1A coding variants were associated with higher low-density lipoprotein cholesterol, apolipoprotein B, creatinine, and fibrinogen in EA. We replicated the associations between HNF1A coding variants and C-reactive protein, fibrinogen, low-density lipoprotein cholesterol, and renal function in a second population-based sample of EA adults 65 years and older from the Cardiovascular Health Study. The HNF1A Ser486Asn and/or Ile27Leu variants were also associated with increased risk of subclinical coronary atherosclerosis in Coronary Artery Risk Development in Young Adults and with incident coronary heart disease in Cardiovascular Health Study. The Ile27Leu and Ser486Asn variants were 3-fold less common in AA than in EA. There was little evidence of association between HNF1A genotype and atherosclerosis-related phenotypes in AA.
CONCLUSIONS
Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.
背景
转录因子肝细胞核因子（HNF）-1α调节许多参与先天免疫、血液凝固、脂质和葡萄糖转运与代谢以及细胞解毒的基因的活性。HNF-1α基因（HNF1A）的常见多态性最近与中年至老年欧裔美国人（EA）的血浆C反应蛋白和γ-谷氨酰转移酶浓度相关。
方法与结果
我们在基于人群的大型青年成人冠状动脉风险发展研究中，评估了HNF1A的常见变异是否与C反应蛋白、γ-谷氨酰转移酶以及其他动脉粥样硬化和代谢风险因素相关，该研究纳入了健康的年轻EA成年人（n = 2154）和非裔美国（AA；n = 2083）成年人。在EA中，Ile27Leu（rs1169288）和Ser486Asn（rs2464196）的次要等位基因与C反应蛋白和γ-谷氨酰转移酶水平降低0.10至0.15标准差单位相关。相同的HNF1A编码变异与EA中较高的低密度脂蛋白胆固醇、载脂蛋白B、肌酐和纤维蛋白原相关。我们在心血管健康研究中来自65岁及以上EA成年人的第二个基于人群的样本中，重复了HNF1A编码变异与C反应蛋白、纤维蛋白原、低密度脂蛋白胆固醇和肾功能之间的关联。在青年成人冠状动脉风险发展研究中，HNF1A Ser486Asn和/或Ile27Leu变异也与亚临床冠状动脉粥样硬化风险增加相关，在心血管健康研究中与冠心病发病相关。Ile27Leu和Ser486Asn变异在AA中的常见程度比在EA中低3倍。在AA中，几乎没有证据表明HNF1A基因型与动脉粥样硬化相关表型之间存在关联。
结论
HNF1A的常见多态性似乎影响年轻和老年EA成年人总体人群中与心血管风险相关的多种表型。
Zotero 插件