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
Year: 2009
Type: article
Study design: Observational Study
Abstract: 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.
Institutions: University of Vermont, University of North Carolina at Chapel Hill, University of Minnesota, Mayo Clinic, Johns Hopkins University, University of Washington, Johns Hopkins Medicine, University of Alabama at Birmingham, Fred Hutch Cancer Center, UAB Medicine, The University of Texas Health Science Center at Houston
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: bronze
Awards: CARDIA, G1023702118, G10717269, G1220223050, G1241292848, G125972088, CORONARY HEART DISEASE AND STROKE, G1275353700, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CHS-ULTRASOUND READING, CARDIA, CORONARY HEART DISEASE AND STROKE, G1639455850, MRI READING CENTER FOR THE CARDIOVASCULAR HEALTH STUDY, CARDIA, G1811124596, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, G191650467, G1962815341, CARDIA-ECHOCARDIOGRAPHY READING, G2194386449, CORONARY HEART DISEASE AND STROKE IN PEOPLE AGED 65-84, CORONARY HEART DISEASE &STROKE IN PEOPLE AGED 65-84, CARDIA, CORONARY HEART DISEASE &STROKE IN THE ELDERLY, G270907595, G277826483, G2800149121, G2999469019, G3107571658, CORONARY ARTERY DISEASE RISK DEVELOPMENT IN YOUNG ADULTS, G3226848658, G328935669, G3396487927, G34347772, G3640229131, CENTRAL BLOOD ANALYSIS LABORATORY FOR CHS, Inflammation Genomics and Atherosclerosis, G4048755144, G4165892905, G423252844, Coronary Artery Risk Development in Young Adults (CARDIA) Study - Field Center, G50822097, G510023084, G5452216648, G582705428, CHS Events Follow-up Study, G6226795708, Epidemiology: Oxidative Stress and Early Atherosclerosis, G6520056932, G6639375596, CHS-Transition Phase, G715477388, CHS RETINAL READING CENTER, CARDIOVASCULAR HEALTH STUDY--ECHOCARDIOGRAPHY, G7999488110, G8593276544, UW-FHCRC Variation Discovery Resource, G905887895, G936067872
OpenAlex ID: W2120011811