medigraphic.com
ISSN 0188-9796 (Print)

2008, Number 1

<< Back Next >>

Rev Endocrinol Nutr 2008; 16 (1)

Genetic sides of the familial combined hyperlipidemia

Huertas-Vázquez A

Language: Spanish
References: 83
Page: 16-23
PDF size: 142.25 Kb.


ABSTRACT

Familial combined hyperlipidemia is a common genetic disorder that increases the risk of premature coronary heart disease. Familial combined hyperlipidemia is characterized by a variable expression of hypercholesterolemia and/or hypertriglyceridemia. Genetic studies have been conducted in different populations to identify chromosomal regions and genetic variants that confer susceptibility for the familial combined hyperlipidemia phenotype. This review focuses of the genetic bases of this common dyslipidemia and addresses the progress in the identification of susceptibility genes involved in familial combined hyperlipidemia in Mexican families.


REFERENCES

  1. 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 1973; 52: 1544-68.

  2. Nikkila EA, Aro A. Family study of serum lipids and lipoproteins in coronary heart-disease. Lancet 1973; 1: 954–59.

  3. Rose HG, Kranz P, Weinstock M, Juliano J, Haft J. Inheritance of combined hyperlipoproteinemia: evidence for a new lipoprotein phenotype. Am J Med 1973; 54: 148-60.

  4. De Graaf J, Stalenhoef AF. Defects of lipoprotein metabolism in familial combined hyperlipidaemia. Curr Opin Lipidol 1998; 9: 189-96.

  5. Sniderman A, Brown G, Stewart F, Cianflone K. From familial combined hyperlipidaemia to hyperapo B: untravelling of overproduction of hepatic apolipoprotein B. Curr Opin Lipidol 1992; 3: 137-42.

  6. Venkatesan S, Cullen P, Pacy P, Halliday D, Scott J. Stable isotopes show a direct relation between VLDL apoB overproduction and serum triglyceride levels and indicate a metabolically and biochemically coherent basis for familial combined hyperlipidemia. Arterioscler Thromb 1993; 13: 1110-18.

  7. Brunzell JD, Albers JJ, Chait A, Grundy SM, Groszek E, McDonald GB. Plasma lipoproteins in familial combined hyperlipidemia and monogenic familial hypertriglyceridemia. J Lipid Res 1983; 24: 147-55.

  8. Bredie SJ, Demacker PN, Stalenhoef AF. Metabolic and genetic aspects of familial combined hyperlipidaemia with emphasis on low-density lipoprotein heterogeneity. Eur J Clin Invest 1997; 27: 802-11.

  9. Porkka KV, Nuotio I, Pajukanta P, Ehnholm C, Suurinkeroinen L, Syvanne M, Lehtimaki T, Lahdenkari AT, Lahdenpera S, Ylitalo K, Antikainen M, Perola M, Raitakari OT, Kovanen P, Viikari JS, Peltonen L, Taskinen MR. Phenotype expression in familial combined hyperlipidemia. Atherosclerosis 1997; 133: 245-53.

  10. Cortner JA, Coates PM, Bennett MJ, Cryer DR, Le NA. Familial combined hyperlipidaemia: use of stable isotopes to demonstrate overproduction of very low-density lipoprotein apolipoprotein B by the liver. J Inherit Metab Dis 1991; 14: 915-22.

  11. Aguilar-Salinas CA, Hugh P, Barret R, Pulsi J, Zhu XL, Schonfeld G. A familial combined hyperlipidemic kindred with impaired apolipoprotein B catabolism: kinetics of apolipoprotein B during placebo and pravastatin therapy. Arterioscler Thromb Vasc Biol 1997; 17: 72-82.

  12. De Graaf J, Stalenhoef AF. Defects of lipoprotein metabolism in familial combined hyperlipidaemia. Curr Opin Lipidol 1998; 9: 189-96.

  13. 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 2004; 36: 371-76.

  14. 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 2001; 42: 1298-1307.

  15. Pajukanta P, Terwilliger JD, Perola M, Hiekkalinna T, Nuotio I, Ellonen P, Parkkonen M, Hartiala J, Ylitalo K, Pihlajamäki J, Porkka K, Laakso M, Viikari J, Ehnholm C, Taskinen MJ, 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 1999; 64: 1453-63.

  16. Aouizerat BE, Allayee H, Cantor RM, Davis RD, Lanning C, Wen P, Dallinga-Thie G, De Bruin T, Rotter JI, Lusis AJ. A genome scan for familial combined hyperlipidemia reveals evidence of linkage with a locus on chromosome 11. Am J Hum Genet 1999; 65: 397-412.

  17. Naoumova RP, Bonney SA, Eichenbaum-Voline S, Patel HN, Jones B, Jones EL, Amey J, Colilla S, Neuwirth CK, Allotey R, Seed M, Betteridge DJ, Galton DJ, Cox NJ, Bell GI, Scott J, Shoulders CC. Confirmed locus on chromosome 11p and candidate loci on 6q and 8p for the triglyceride and cholesterol traits of combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2003; 23: 2070-77.

  18. 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 1998; 18: 369-73.

  19. Pei W, Baron H, Muller-Myhsok B, Knoblauch H, Al-Yahyaee SA, Hui R, Wu X, Liu L, Busjahn A, Luft FC, Schuster H. Support for linkage of familial combined hyperlipidemia to chromosome 1q21-q23 in Chinese and German families. Clin Genet 2000; 57: 29-34.

  20. Coon H, Myers RH, Borecki IB, Arnett DK, Hunt SC, Province MA, Djousse L, Leppert MF. Replication of linkage of familial combined hyperlipidemia to chromosome 1q with additional heterogeneous effect of apolipoprotein A-I/C-III/A-IV locus: the NHLBI Family Heart Study. Arterioscler Thromb Vasc Biol 2000; 20: 2275-80.

  21. Huertas-Vázquez A, del Rincón JP, Canizales-Quinteros S, Riba L, Vega-Hernández G, Ramírez-Jiménez S, Auron-Gómez M, Gómez-Pórez FJ, Aguilar-Salinas CA, Tusie-Luna MT. Contribution of chromosome 1q21-q23 to familial combined hyperlipidemia in Mexican families. Ann Hum Genet 2004; 68: 419-27.

  22. Hanson RL, Ehm MG, Pettitt DJ, Prochazka M, Thompson DB, Timberlake D, Foroud T, Kobes S, Baier L, Burns DK, Almasy L, Blangero J, Garvey WT, Bennett PH, Knowler WC. An autosomal genomic scan for loci linked to type II diabetes mellitus and body mass index in Pima Indians. Am J Hum Genet 1998; 63: 1130-38.

  23. Elbein SC, Hoffman MD, Teng K, Leppert MF, Hasstedt SJ. A genome-wide search for type 2 diabetes susceptibility genes in Utah Caucasians. Diabetes 1999; 48: 1175-82.

  24. Vionnet N, Hani El-H, Dupont S, Gallina S, Francke S, Dotte S, De Matos F, Durand E, Lepretre F, Lecoeur C, Gallina P, Zekiri L, Dina C, Froguel P. Genomewide Search for Type 2 Diabetessusceptibility genes in French whites: Evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and Independent Replication of a Type 2Diabetes Locus on Chromosome 1q21q24. Am J Hum Genet 2000; 67: 1470-80.

  25. Wiltshire S, Hattersley AT, Hitman GA, Walker M, Levy JC, Sampson M, O’Rahilly S, Frayling TM, Bell JI, Lathrop GM, Bennett A, Ranjit Dhillon, Fletcher C, Groves JC, Jones E, Prestwich P, Simecek N, Pamidighantam V, Subba Rao, Wishart M, Foxon R, Howell S, Smedley D, Cardon LR, Menzel S, McCarthy MI: A Genomewide Scan for Loci Predisposing to Type 2 Diabetes in a U.K. Population (The Diabetes UK Warren 2 Repository): Analysis of 573 Pedigrees Provides Independent Replication of a Susceptibility Locus on Chromosome 1q. Am J Hum Genet 2001; 69: 553-69.

  26. Wen-Chi H, St. Jean PL, Mitchell BD, Pollin TI, Knowler WC, Ehm MG, Bell CJ, Sakul H, Wagner MJ, Burns DK, Shuldiner AR. Genome-wide and fine-mapping linkage studies of type 2 diabetes and glucose traits in the old order amish evidence for a new diabetes locus on chromosome 14q11 and confirmation of a locus on chromosome 1q21-q24. Diabetes 2003; 52: 550-7.

  27. Maggie CYNg, Wing-Yee So, Lam VKL, Cockram CS, Bell GI, Cox NJ, Chan JCN. Genome-wide scan for metabolic syndrome and related quantitative traits in Hong Kong Chinese and confirmation of a susceptibility locus on chromosome 1q21-q25. Diabetes 2004; 53: 2676-683.

  28. Langefeld CD, Wagenknecht LE, Rotter JI, Williams AH, Hokanson JE, Saad MF, Bowden DW, Haffner S, Norris JM, Rich SS, Mitchell BD. Linkage of the Metabolic Syndrome to 1q23-q31 in Hispanic Families. The Insulin Resistance Atherosclerosis Study Family Study. Diabetes 2004; 53: 1170-4.

  29. Huertas-Vázquez A, Aguilar-Salinas C, Lusis AJ, Cantor RM, Canizales-Quinteros S, Lee JC, Mariana-Nunez L, Riba-Ramírez 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 2005; 25: 1985-91.

  30. Mahaney M, Almasy L, Rainwater, VandeBerg J, Cole S, Hixson J, Blangero J, MacCluer JW. A quantitative trait locus on chromosome 16q influences variation in plasma HDL-C Levels in Mexican-Americans. Arterioscler Thromb and Vasc Biol 2003; 23: 339-45.

  31. Wojciechowski AP, Farrall M, Cullen P, Wilson TM, Bayliss JD, Farren B, Griffin BA, Caslake MJ, Packard CJ, Shepherd J. Familial combined hyperlipidaemia linked to the apolipoprotein AI-CII-AIV gene cluster on chromosome 11q23-q24. Nature 1991; 349: 161-64.

  32. Xu CF, Talmud P, Schuster H, Houlston R, Miller G, Humphries S: Association between genetic variation at the APO AI-CIII-AIV gene cluster and familial combined hyperlipidaemia. Clin Genet 1994; 46: 385-97.

  33. Deeb SS, Nevin DN, Iwasaki L, Brunzell JD. Two novel apolipoprotein A-IV variants in individuals with familial combined hyperlipidemia and diminished levels of lipoprotein lipase activity. Hum Mutat 1996; 8: 319-25.

  34. Dallinga-Thie GM, van Linde-Sibenius, TM, Rotter JI, Cantor RM, Bu XD, Lusis AJ, de Bruin TWA. Complex genetic contribution of the apoAI-CIII-AIV gene cluster to familial combined hyperlipidemia. Identification of different susceptibility haplotypes. J Clin Invest 1997; 99: 953-61.

  35. Mar R, Pajukanta P, Allayee H, Groenendijk M, Dallinga-Thie G, Krauss RM, Sinsheimer JS, Cantor RM, de Bruin TW, Lusis AJ. Association of the apolipoprotein A1/C3/A4/A5 gene cluster with triglyceride levels and LDL particle size in familial combined hyperlipidemia. Circ Res 2004; 94: 993-99.

  36. Eichenbaum-Voline S, Olivier M, Jones EL, Naoumova RP, Jones B, Gau B, Patel HN, Seed M, Betteridge DJ, Galton DJ, Rubin EM, Scott J, Shoulders CC, Pennacchio LA. Linkage and association between distinct variants of the APOA1/C3/A4/A5 gene cluster and familial combined hyperlipidemia. Arterioscler Thromb Vasc Biol 2004; 24: 167-74.

  37. Gagne E, Genest J Jr, Zhang H, Clarke LA, Hayden MR. Analysis of DNA changes in the LPL gene in patients with familial combined hyperlipidemia. Arterioscler Thromb 1994; 14: 1250-57.

  38. Reymer PW, Groenemeyer BE, Gagne E, Miao L, Appelman EE, Seidel JC, Kromhout D, Bijvoet SM, van de Oever K, de Bruin TW. A frequently occurring mutation in the lipoprotein lipase gen (Asn291Ser) contributes to the expression of familial combined hyperlipidemia. Hum Mol Genet 1995; 4: 1543-49.

  39. De Bruin TW, Mailly F, van Barlingen HH, Fisher R, Castro CM, Talmud P, Dallinga-Thie GM, Humphries SE. Lipoprotein lipase gene mutations D9N and N291S in four pedigrees with familial combined hyperlipidaemia. Eur J Clin Invest 1996; 26: 631-39.

  40. Hoffer MJ, Bredie SJ, Snieder H, Reymer PW, Demacker PN, Havekes LM, Boomsma DI, Stalenhoef AF, Frants RR, Kastelein JJ. Gender-related association between the -93T—>G/D9N haplotype of the lipoprotein lipase gene and elevated lipid levels in familial combined hyperlipidemia. Atherosclerosis 1998; 138: 91-9.

  41. Campagna AM, Baroni M, Maria A, Ricci G, Antonini R, Verna R, Arca M. Common variants in the lipoprotein lipase gene, but not those in the insulin receptor substrate[ndash ]1, the [beta]-adrenergic receptor, and the intestinal fatty acid binding protein-2 genes, influence the lipid phenotypic expression in familial combined hyperlipidemia. Metabolism 2002; 51: 1298-1305.

  42. Gehrisch S, Kostka H, Tiebel M, Patzak A, Paetzold A, Julius U, Schroeder HE, Hanefeld M, Jaross W. Mutations of the human hepatic lipase gene in patients with combined hypertriglyceridemia/hyperalphalipoproteinemia and in patients with familial combined hyperlipidemia. J Mol Med 1999; 77: 728-34.

  43. Allayee H, Dominguez KM, Aouizerat BE, Krauss RM, Rotter JI, Lu J, Cantor RM, de Bruin TW, Lusis AJ. Contribution of the hepatic lipase gene to the atherogenic lipoprotein phenotype in familial combined hyperlipidemia. J Lipid Res 2000; 41: 245-52.

  44. Allayee H, Aouizerat BE, Cantor RM, Dallinga-Thie GM, Krauss RM, Lanning CD, Rotter JI, Lusis AJ, de Bruin TW. Families with familial combined hyperlipidemia and families enriched for coronary artery disease share genetic determinants for the atherogenic lipoprotein phenotype. Am J Hum Genet 1998; 63: 577-85.

  45. Aouizerat BE, Allayee H, Bodnar J, Krass KL, Peltonen L, de Bruin TW, Rotter JI, Lusis AJ. Novel genes for familial combined hyperlipidemia. Curr Opin Lipidol 1999; 10: 113-122.

  46. Geurts JM, Janssen RG, van Greevenbroek MM, van der Kallen CJ, Cantor RM, Bu X, Aouizerat BE, Allayee H, Rotter JI, de Bruin TW. Identification of TNFRSF1B as a novel modifier gene in familial combined hyperlipidemia. Hum Mol Genet 2000; 9: 2067-74.

  47. Vallet VS, Casado M, Henrion AA, Bucchini D, Raymondjean M, Kahn A, Vaulont S. Differential roles of upstream stimulatory factors 1 and 2 in the transcriptional response of liver genes to glucose. J Biol Chem 1998; 273: 20175-79.

  48. Casado M, Vallet VS, Kahn A, Vaulont S. Essential role in vivo of upstream stimulatory factors for a normal dietary response of the fatty acid synthase gene in the liver. J Biol Chem 1999; 274: 2009-13.

  49. Ribeiro A, Pastier D, Kardassis D, Chambaz J, Cardot P. Cooperative binding of upstream stimulatory factor and hepatic nuclear factor 4 drives the transcription of the human apolipoprotein A-II gene. J Biol Chem 1995; 274: 1216-25.

  50. Pastier D, Lacorte JM, Chambaz J, Cardot P, Ribeiro A. Two initiator like elements are required for the combined activation of the human apolipoprotein C-III promoter by upstream stimulatory factor and hepatic nuclear factor-4. J Biol Chem 2002; 277: 15199-206.

  51. Iynedjian PB. Identification of upstream stimulatory factor as transcriptional activator of the liver promoter of the glucokinase gene. Biochem J 1998; 333: 705-12.

  52. Kutz SM, Higgins CE, Samarakoon R, Higgins SP, Allen RR, Qi L, Higgins P. TGF-beta-induced PAI-1 expression is E box/USF-dependent and requires EGFR signaling. Exp Cell Res 2006; 312: 1093-1105.

  53. Yang XP, Freeman LA, Knapper CL, Amar MJ, Remaley A, Brewer HB Jr, Santamarina-Fojo S. The E-box motif in the proximal ABCA1 promoter mediates transcriptional repression of the ABCA1 gene. J Lipid Res 2002; 43: 297-306.

  54. Wang D, Sul HS. Upstream stimulatory factor binding to the E-box at -65 is required for insulin regulation of the fatty acid synthase promoter. J Biol Chem 1997; 272: 26367-374.

  55. Botma GJ, Verhoeven AJ, Jansen H. Hepatic lipase promoter activity is reduced by the C-480T and G-216A substitutions present in the common LIPC gene variant and is increased by Upstream Stimulatory Factor. Atherosclerosis 2001; 154: 625-32.

  56. Salero E, Gimenez C, Zafra F. Identification of a non-canonical E-box motif as a regulatory element in the proximal promoter region of the apolipoprotein E gene. Biochem J 2003; 370: 979-86.

  57. Nowak M, Helleboid-Chapman A, Jakel H, Martin G, Duran-Sandoval D, Staels B, Rubin EM, Pennacchio LA, Taskinen MR, Fruchart-Najib J, Fruchart JC. Insulin-mediated down-regulation of apolipoprotein A5 gene expression through the phosphatidylinositol 3-kinase pathway: role of upstream stimulatory factor. Mol Cell Biol 2005; 25: 1537-48.

  58. Portois L, Tastenoy M, Viollet B, Svoboda M. Functional analysis of the glucose response element of the rat glucagon receptor gene in insulin-producing INS-1 cells. Biochim Biophys Acta 2002; 1574: 175-86.

  59. Read ML, Clark AR, Docherty K. The helix-loop-helix transcription factor USF (upstream stimulating factor) binds to a regulatory sequence of the human insulin gene enhancer. Biochem J 1993; 295: 233-37.

  60. Martin CC, Svitek CA, Oeser JK, Henderson E, Stein R, O’Brien RM. Upstream stimulatory factor (USF) and neurogenic differentiation/beta-cell E box transactivator 2 (NeuroD/BETA2) contribute to islet-specific glucose-6-phosphatase catalytic-subunit-related protein (IGRP) gene expression. Biochem J 2003; 371: 6752-786.

  61. Travers MT, Vallance AJ, Gourlay HT, Gill CA, Klein I, Bottema C, Barber MC. Promoter I of the ovine acetyl-CoA carboxylase-alpha gene: an E-box motif at-114 in the proximal promoter binds upstream stimulatory factor (USF)-1 and USF-2 and acts as an insulin-response sequence in differentiating adipocytes. Biochem J 2001; 359: 273-84.

  62. Smih F, Rouet P, Lucas S, Mairal A, Sengenes C, Sengenes LM, Vaulont S, Casado M, Langin D. Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose. Diabetes 2002; 51: 293–300.

  63. Van der VGM, Hijmans AIA, van Duijn CM, Stalenhoef AF, de Graaf J: The involvement of upstream stimulatory factor 1 in Dutch patients with familial combined hyperlipidemia. J lipid Res 2007;48:193-200.

  64. Putt W, Palmen J, Nicaud V, Tregouet DA, Tahri-Daizadeh NF, Humphries SE, Talmud PJ, EARSII group. Variation in USF1 shows haplotype effects, gene:gene and gene: environment associations with glucose and lipid parameters in the European Atherosclerosis Research Study II. Hum Mol Genet 2004; 13: 1587-97.

  65. 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 2005; 117: 444-51.

  66. Ng, MC, Miyake K, So WY, Poon EW, Lam VK, Li JK Ng MC, Cox NJ, Bell GI, Chan JC. The linkage and association of the gene encoding upstream stimulatory factor 1 with type 2 diabetes and metabolic syndrome in the Chinese population. Diabetologia 2005; 48: 2018-24.

  67. Gibson F, Hercberg S, Froguel P. Common polymorphisms in the USF1 gene are not associated with type 2 diabetes in French Caucasians. Diabetes 2005; 54: 3040-42.

  68. Zeggini E, Damcott CM, Hanson RL, Karim MA, Rayner NW, Groves CJ, Baier LJ, Hale TC, Hattersley AT, Hitman GA, Hunt SE, Knowler WC, Mitchell BD, Ng MC, O’Connell JR, Pollin TI, Vaxillaire M, Walker M, Wang X, Whittaker P, Xiang K, Jia W, Chan JC, Froguel P, Deloukas P, Shuldiner AR, Elbein SC, McCarthy MI. International Type 2 Diabetes 1q Consortium: Variation within the gene encoding the upstream stimulatory factor 1 does not influence susceptibility to type 2 diabetes in samples from populations with replicated evidence of linkage to chromosome 1q. Diabetes 2006; 55: 2541-48.

  69. Komulainen K, Alanne M, Auro K, Kilpikari R, Pajukanta P, Saarela J, Ellonen P, Salminen K, Kulathinal S, Kuulasmaa K, Silander K, Salomaa V, Perola M, Peltonen L. Risk Alleles of USF1-gene predict cardiovascular disease of women in two prospective studies. PLoS Genet 2006; 2: 672-81.

  70. Hoffstedt J, Ryden M, Wahrenberg H, van Harmelen V, Arner P: Upstream transcription factor-1 gene polymorphism is associated with increased adipocyte lipolysis. J Clin Endocrinol Metab 2005; 90: 5356-60.

  71. Naukkarinen J, Gentile M, Soro-Paavonen A, Saarela J, Koistinen HA, Pajukanta P, Taskinen MR, Peltonen L. USF1 and dyslipidemias: converging evidence for a functional intronic variants. Hum Mol Genet 2005; 14: 2595-2605.

  72. 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 1996; 384: 458-60.

  73. 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 2004; 53: 1134-40.

  74. 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-4a are associated with type 2 diabetes in the Amish. Diabetes 2004; 53: 3337-41.

  75. 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 2005; 48: 452-58.

  76. 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-4 gene predicts susceptibility to type 2 diabetes. Diabetes 2004; 53: 1141-49.

  77. 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-4a gene with risk of type 2 diabetes in 7,883 people. Diabetes 2005; 54: 886-92.

  78. Perusse L, Chagnon YC, Dionne FT, Bouchard C. The human obesity gene map: the 1996 update. Obes Res 1997; 5: 49-61.

  79. Lee JH, Reed DR, Li WD, Xu W, Joo EJ, Kilker RL, Nanthakumar E, North M, Sakul H, Bell C, Price RA. Genome scan for human obesity and linkage to markers in 20q13. Am J Hum Genet 1999; 64: 196-209.

  80. Dong C, Wang S, Li WD, Li D, Zhao H, Price RA. Interacting genetic loci on chromosomes 20 and 10 influence extreme human obesity. Am J Hum Genet 2003; 72: 115-124.

  81. 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 2002; 70: 1333-40.

  82. Weissglas-Volkov D, Huertas-Vázquez A, Suviolahti E, Lee J, Plaisier C, Canizales-Quinteros S, Tusie-Luna T, Aguilar-Salinas C, Taskinen MR, Pajukanta P. Common hepatic nuclear factor 4 alpha variants are associated with high serum lipid levels and the metabolic syndrome. Diabetes 2006; 55: 1970-77.

  83. 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 2005; 14: 3435-47.




2020     |     www.medigraphic.com