You are here
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 Cardiovascula
Tuesday,2012-11-06 12:19 America/Los_Angeles — eenright
| Title | 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 Cardiovascula |
| Publication Type | Journal Article |
| Year of Publication | 2009 |
| Authors | Reiner, AP, Gross, MD, Carlson, CS, Bielinski, SJ, Lange, LA, Fornage, M, Jenny, NS, Walston, J, Tracy, RP, O Williams, D, Jacobs, DR, Nickerson, DA |
| Journal | Circ Cardiovasc Genet |
| Volume | 2 |
| Issue | 3 |
| Pagination | 244-54 |
| Date Published | 2009 Jun |
| ISSN | 1942-3268 |
| Keywords | Adolescent, Adult, African Americans, Aged, Aged, 80 and over, C-Reactive Protein, Cardiovascular Diseases, Cholesterol, LDL, Cohort Studies, European Continental Ancestry Group, Female, Fibrinogen, gamma-Glutamyltransferase, Genetic Predisposition to Disease, Genotype, Hepatocyte Nuclear Factor 1-alpha, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Risk Factors |
| Abstract | <p><b>BACKGROUND: </b>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).</p><p><b>METHODS AND RESULTS: </b>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.</p><p><b>CONCLUSIONS: </b>Common polymorphisms of HNF1A seem to influence multiple phenotypes related to cardiovascular risk in the general population of younger and older EA adults.</p> |
| DOI | 10.1161/CIRCGENETICS.108.839506 |
| Alternate Journal | Circ Cardiovasc Genet |
| PubMed ID | 20031592 |
| PubMed Central ID | PMC2841292 |
| Grant List | R01 HL071862-05A1 / HL / NHLBI NIH HHS / United States U01 HL066642 / HL / NHLBI NIH HHS / United States R01 HL071017 / HL / NHLBI NIH HHS / United States N01-HC-05187 / HC / NHLBI NIH HHS / United States R01 HL053560 / HL / NHLBI NIH HHS / United States HL71017 / HL / NHLBI NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-48047 / HC / NHLBI NIH HHS / United States N01HC48049 / HL / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-95095 / HC / NHLBI NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States N01-HC-48050 / HC / NHLBI NIH HHS / United States 1R01-HL53560-01A1 / HL / NHLBI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01HC95095 / HL / NHLBI NIH HHS / United States N01-HC-48049 / HC / NHLBI NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01 HC045134 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States R01 HL071862 / HL / NHLBI NIH HHS / United States N01HC48050 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States N01HC05187 / HL / NHLBI NIH HHS / United States N01HC48047 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States HL66682 / HL / NHLBI NIH HHS / United States N01-HC-48048 / HC / NHLBI NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States HL66642 / HL / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States U01 HL066682 / HL / NHLBI NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States N01HC48048 / HL / NHLBI NIH HHS / United States |