Common hepatic nuclear factor-4α variants are associated with high serum lipid levels and the metabolic syndrome

Diabetes

Volumn 55, Issue 7, 2006, Pages 1970-1977

  Weissglas Volkov, Daphna ^a   Huertas Vazquez, Adriana ^a   Suviolahti, Elina ^a   Lee, Jenny ^a   Plaisier, Christopher ^a   Canizales Quinteros, Samuel ^b   Tusie Luna, Teresa ^b   Aguilar Salinas, Carlos ^c   Taskinen, Marja Riitta ^d   Pajukanta, Päivi ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSIDAD NACIONAL AUTÓNOMA DE MÉXICO   (Mexico)

^c INSTITUTO NACIONAL DE CIENCIAS MÉDICAS Y NUTRICIÓN SALVADOR ZUBIRÁN   (Mexico)

^d HELSINKI UNIVERSITY CENTRAL HOSPITAL   (Finland)

Author keywords

Apo, apolipoprotein; AUC, area under the curve; CHD, coronary heart disease; FBAT, family based association test; FCHL, familial combined hyperlipidemia; HBAT, haplotype based association test; Hepatic nuclear factor 4 ; HNF 4

Indexed keywords

HEPATIC NUCLEAR FACTOR 4 ALPHA; LIPID; NUCLEAR FACTOR; UNCLASSIFIED DRUG; APOLIPOPROTEIN B; CHOLESTEROL; HEPATOCYTE NUCLEAR FACTOR 4; HNF4A PROTEIN, HUMAN; TRIACYLGLYCEROL;

ARTICLE; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; HAPLOTYPE; HUMAN; LIPID ANALYSIS; LIPID BLOOD LEVEL; MAJOR CLINICAL STUDY; METABOLIC SYNDROME X; PRIORITY JOURNAL; BLOOD; CLINICAL TRIAL; COMPARATIVE STUDY; FINLAND; GENE FREQUENCY; GENETIC VARIABILITY; GENETICS; HYPERLIPIDEMIA; MEXICO; MULTICENTER STUDY; NON INSULIN DEPENDENT DIABETES MELLITUS; PHENOTYPE; SINGLE NUCLEOTIDE POLYMORPHISM;

APOLIPOPROTEINS B; CHOLESTEROL; DIABETES MELLITUS, TYPE 2; FINLAND; GENE FREQUENCY; HEPATOCYTE NUCLEAR FACTOR 4; HUMANS; HYPERLIPIDEMIAS; METABOLIC SYNDROME X; MEXICO; PHENOTYPE; POLYMORPHISM, SINGLE NUCLEOTIDE; TRIGLYCERIDES; VARIATION (GENETICS);

EID: 33747039577     PISSN: 00121797     EISSN: 00121797     Source Type: Journal    
DOI: 10.2337/db06-0035     Document Type: Article

References (45)

1. Love-Gregory LD, Wasson J, Ma J, Jin CH, Glaser B, Suarez BK, Permutt MA: A common polymorphism in the upstream promoter region of the hepatocyte nuclear factor 4 alpha gene on chromosome 20q is associated with type 2 diabetes and appears to contribute to the evidence for linkage in an Ashkenazi Jewish population. Diabetes 53:1134-1140, 2004
2. Damcott CM, Hoppman N, Ott SH, Reinhart LJ, Wang J, Pollin TI, O'Connell JR, Mitchell BD, Shuldiner AR: Polymorphisms in both promoters of hepatocyte nuclear factor 4-α are associated with type 2 diabetes in the Amish. Diabetes 53:3337-3341, 2004
3. Hansen SK, Rose CS, Glumer C, Drivsholm T, Borch-Johnsen K, Jorgensen T, Pedersen O, Hansen T: Variation near the hepatocyte nuclear factor (HNF)-4alpha gene associates with type 2 diabetes in the Danish population. Diabetologia 48:452-458, 2005
4. Silander K, Mohlke KL, Scott LJ, Peck EC, Hollstein P, Skol AD, Jackson AU, Deloukas P, Hunt S, Stavrides G, Chines PS, Erdos MR, Narisu N, Conneely KN, Li C, Fingerlin TE, Dhanjal SK, Valle TT, Bergman RN, Tuomilehto J, Watanabe RM, Boehnke M, Collins FS: Genetic variation near the hepatocyte nuclear factor-4α gene predicts susceptibility to type 2 diabetes. Diabetes 53:1141-1149, 2004
5. Winckler W, Graham RR, de Bakker PI, Sun M, Almgren P, Tuomi T, Gaudet D, Hudson TJ, Ardlie KG, Daly MJ, Hirschhorn JN, Groop L, Altshuler D: Association testing of variants in the hepatocyte nuclear factor-4α gene with risk of type 2 diabetes in 7,883 people. Diabetes 54:886-892, 2005
6. Yamagata K, Furuta H, Oda N, Kaisaki PJ, Menzel S, Cox NJ, Fajans SS, Signorini S, Stoffel M, Bell GI: Mutations in the hepatocyte nuclear factor 4, alpha gene in maturity-onset diabetes of the young (MODY1). Nature 384:458-460, 1996
7. Sladek FM, Seidel S: Hepatocyte nuclear factor 4a. In Nuclear Receptors and Genetic Disease. Burris TP, McCabeed, Eds. London, Academic Press, 2001
8. Thomas H, Jaschkowitz K, Bulman M, Frayling TM, Mitchell SM, Roosen S, Lingott-Frieg A, Tack CJ, Ellard S, Ryffel GU, Hattersley AT: A distant upstream promoter of the HNF-4 alpha gene connects the transcription factors involved in maturity-onset diabetes of the young. Hum Mol Genet 10:2089-2097, 2001
9. Nakhei H, Lingott A, Lemm I, Ryffel GU: An alternative splice variant of the tissue specific transcription factor HNF-4 alpha predominates in undifferentiated murine cell types. Nucleic Acid Res 26:497-504, 1998
10. Grundy SM, Chait A, Brunzell JD: Familial combined hyperlipidemia workshop. Arteriosclerosis 7:203-207, 1989
11. Goldstein JL, Schrott HG, Hazzard WR, Bierman EL, Motulsky AG: Hyperlipidemia in coronary heart disease. II. Genetic analysis of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 52:1544-1568, 1973
12. Vakkilainen J, Porkka KV, Nuotio I, Pajukanta P, Suurinkeroinen L, Ylitalo K, Viikari JS, Ehnholm C, Taskinen MR: Glucose intolerance in familial combined hyperlipidaemia: EUFAM Study Group. Eur J Clin Invest 28:24-32, 1998
13. Nikkilä EA, Aro A: Family study of serum lipids and lipoproteins in coronary heart-disease. Lancet 1:954-959, 1973
14. Pajukanta P, Nuotio I, Terwilliger JD, Porkka KV, Ylitalo K, Pihlajamaki J, Suomalainen AJ, Syvanen AC, Lehtimaki T, Viikari JS, Laakso M, Taskinen MR, Ehnholm C, Peltonen L: Linkage of familial combined hyperlipidaemia to chromosome 1q21-q23. Nat Genet 18:369-373, 1998
15. Soro A, Pajukanta P, Lilja HE, Ylitalo K, Hiekkalinna T, Perola M, Cantor RM, Viikari JS, Taskinen MR, Peltonen L: Genome scans provide evidence for low-HDL-C loci on chromosomes 8q23, 16q24.1-24.2, and 20q13.11 in Finnish families. Am J Hum Genet 70:1333-1340, 2002
16. Lilja HE, Suviolahti E, Soro-Paavonen A, Hiekkalinna T, Day A, Lange K, Sobel E, Taskinen MR, Peltonen L, Perola M, Pajukanta P: Locus for quantitative HDL-cholesterol on chromosome 10q in Finnish families with dyslipidemia. J Lipid Res 45:1876-1884, 2004
17. Yu Y, Wyszynski DF, Waterworth DM, Wilton SD, Barter PJ, Kesaniemi YA, Mahley RW, McPherson R, Waeber G, Bersot TP, Ma Q, Sharma SS, Montgomery DS, Middleton LT, Sundseth SS, Mooser V, Grundy SM, Farrer LA: Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia. J Lipid Res 46:2202-2213, 2005
18. Li WD, Dong C, Li D, Garrigan C, Price RA: A genome scan for serum triglyceride in obese nuclear families. J Lipid Res 46:432-438, 2005
19. Bowden DW, Sale M, Howard TD, Qadri A, Spray BJ, Rothschild CB, Akots G, Rich SS, Freedman BI: Linkage of genetic markers on human chromosomes 20 and 12 to NIDDM in Caucasian sib pairs with a history of diabetic nephropathy. Diabetes 46:882-886, 1997
20. Ji L, Malecki M, Warram JH, Yang Y, Rich SS, Krolewski AS: New susceptibility locus for NIDDM is localized to human chromosome 20q. Diabetes 46:876-881, 1997
21. Lembertas AV, Perusse L, Chagnon YC, Fisler JS, Warden CH, Purcell-Huynh DA, Dionne FT, Gagnon J, Nadeau A, Lusis AJ, Bouchard C: Identification of an obesity quantitative trait locus on mouse chromosome 2 and evidence of linkage to body fat and insulin on the human homologous region 20q. J Clin Invest 100:1240-1247, 1997
22. Zouali H, Hani EH, Philippi A, Vionnet N, Beckmann JS, Demenais F, Froguel P: A susceptibility locus for early-onset non-insulin dependent (type 2) diabetes mellitus maps to chromosome 20q, proximal to the phosphoenolpyruvate carboxykinase gene. Hum Mol Genet 6:1401-1408, 1997
23. Ghosh S, Watanabe RM, Hauser ER, Valle T, Magnuson VL, Erdos MR, Langefeld CD, Balow J Jr, Ally DS, Kohtamaki K, Chines P, Birznieks G, Kaleta HS, Musick A, Te C, Tannenbaum J, Eldridge W, Shapiro S, Martin C, Witt A, So A, Chang J, Shurtleff B, Porter R, Kudelko K, Unni A, Segal L, Sharaf R, Blaschak-Harvan J, Eriksson J, Tenkula T, Vidgren G, Ehnholm C, Tuomilehto-Wolf E, Hagopian W, Buchanan TA, Tuomilehto J, Bergman RN, Collins FS, Boehnke M: Type 2 diabetes: evidence for linkage on chromosome 20 in 716 Finnish affected sib pairs. Proc Natl Acad Sci U S A 96:2198-2203, 1999
24. Permutt MA, Wasson JC, Suarez BK, Lin J, Thomas J, Meyer J, Lewitzky S, Rennich JS, Parker A, DuPrat L, Maruti S, Chayen S, Glaser B: A genome scan for type 2 diabetes susceptibility loci in a genetically isolated population. Diabetes 50:681-685, 2001
25. Olefsky JM, Farquhar JW, Reaven GM: Reappraisal of the role of insulin in hypertriglyceridemia. Am J Med 57:551-560, 1974
26. Shih DQ, Dansky HM, Fleisher M, Assmann G, Fajans SS, Stoffel M: Genotype/phenotype relationships in HNF-4 α/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein (a), and triglyceride levels. Diabetes 49:832-837, 2000
27. Pajukanta P, Terwilliger JD, Perola M, Hiekkalinna T, Nuotio I, Ellonen P, Parkkonen M, Hartiala J, Ylitalo K, Pihlajamaki J, Porkka K, Laakso M, Viikari J, Ehnholm C, Taskinen MR, Peltonen L: Genomewide scan for familial combined hyperlipidemia genes in Finnish families, suggesting multiple susceptibility loci influencing triglyceride, cholesterol, and apolipoprotein B levels. Am J Hum Genet 64:1453-1463, 1999
28. Huertas-Vazquez A, Aguilar-Salinas C, Lusis AJ, Cantor RM, Canizales-Quinteros S, Lee JC, Mariana-Nunez L, Riba-Ramirez RM, Jokiaho A, Tusie-Luna T, Pajukanta P: Familial combined hyperlipidemia in Mexicans: association with upstream transcription factor 1 and linkage on chromosome 16q24.1. Arterioscler Thromb Vasc Biol 25:1985-1991, 2005
29. Aguilar-Salinas CA, Olaiz G, Valles V, Torres JM, Gomez Perez FJ, Rull JA, Rojas R, Franco A, Sepulveda J: High prevalence of low HDL cholesterol concentrations and mixed hyperlipidemia in a Mexican nationwide survey. J Lipid Res 42:1298-307, 2002
30. World Health Organization: Diabetes Mellitus: Report of a WHO Study Group. Geneva, World Health Org., 1985 (Tech. Rep. Ser., no. 727), p.1-113
31. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III): Executive summary of the Third Report of the National Cholesterol Education Program (NCEP). JAMA 285:2486-2497, 2001
32. Terwilliger JD, Ott J: A haplotype-based 'haplotype relative risk' approach to detecting allelic associations. Hum Hered 42:337-346, 1992
33. Horvath S, Xu X, Lake SL, Silverman EK, Weiss ST, Laird NM: Family-based tests for associating haplotypes with general phenotype data: application to asthma genetics. Genet Epidemiol 26:61-69, 2004
34. Göring HH, Terwilliger JD: Linkage analysis in the presence of error III: marker loci and their map as nuisance parameters. Am J Hum Genet 66:1298-1309, 2000
35. O'Connell JR, Weeks DE: PedCheck: a program for identification of genotype incompatibilities in linkage analysis. Am J Hum Genet 63:259-266, 1998
36. Lathrop GM, Lalouel J-M, Julier CA, Ott J: Strategies for multilocus linkage analysis in humans. Proc Natl Acad Sci U S A 81:3443-3446, 1984
37. Sobel E, Lange K: Descent graphs in pedigree analysis: applications to haplotyping, location scores, and marker-sharing statistics. Am J Hum Genet 58:1323-1337, 1996
38. Terwilliger JD, Haghighi F, Hiekkalinna TS, Göring HH: A biased assessment of the use of SNPs in human complex traits. Curr Opin Genet Dev 12:726-734, 2002
39. Eckel RH, Grundy SM, Zimmet PZ: The metabolic syndrome. Lancet 365:1415-1428, 2005
40. Muller YL, Infante AM, Hanson RL, Love-Gregory L, Knowler W, Bogardus C, Baier LJ: Variants in hepatocyte nuclear factor 4α are modestly associated with type 2 diabetes in Pima Indians. Diabetes 54:3035-3039, 2005
41. Wang H, Maechler P, Antinozzi PA, Hagenfeldt KA, Wollheim CB: Hepatocyte nuclear factor 4alpha regulates the expression of pancreatic beta-cell genes implicated in glucose metabolism and nutrient-induced insulin secretion. J Biol Chem 275:35953-35959, 2000
42. Rhee J, Inoue Y, Yoon JC, Puigserver P, Fan M, Gonzalez FJ, Spiegelman BM: Regulation of hepatic fasting response by PPARgamma coactivator-1alpha (PGC-1): requirement for hepatocyte nuclear factor-4 alpha in gluconeogenesis. Proc Natl Acad Sci U S A 100:4012-4017, 2003
43. Pajukanta P, Lilja HE, Sinsheimer JS, Cantor RM, Lusis AJ, Gentile M, Duan XJ, Soro-Paavonen A, Naukkarinen J, Saarela J, Laakso M, Ehnholm C, Taskinen MR, Peltonen L: Familial combined hyperlipidemia is associated with upstream transcription factor 1 (USF1). Nat Genet 36:371-376, 2004
44. Coon H, Xin Y, Hopkins PN, Cawthon RM, Hasstedt SJ, Hunt SC: Upstream stimulatory factor 1 associated with familial combined hyperlipidemia, LDL cholesterol, and triglycerides. Hum Genet 117:444-451, 2005
45. Rada-Iglesias A, Wallerman O, Koch C, Ameur A, Enroth S, Clelland G, Wester K, Wilcox S, Dovey OM, Ellis PD, Wraight VL, James K, Andrews R, Langford C, Dhami P, Carter N, Vetrie D, Ponten F, Komorowski J, Dunham I, Wadelius C: Binding sites for metabolic disease related transcription factors inferred at base pair resolution by chromatin immunoprecipitation and genomic microarrays. Hum Mol Genet 14:3435-3447, 2005