Dietary fat interacts with the -514C>T polymorphism in the hepatic lipase gene promoter on plasma lipid profiles in a multiethnic Asian population: the 1998 Singapore National Health Survey.

We have previously reported an interaction between -514C>T polymorphism at the hepatic lipase (HL) gene and dietary fat on high-density lipoprotein-cholesterol (HDL-C) metabolism in a representative sample of white subjects participating in the Framingham Heart Study. Replication of these findings in other populations will provide proof for the relevance and consistency of this marker as a tool for risk assessment and more personalized cardiovascular disease prevention. Therefore, we examined this gene-nutrient interaction in a representative sample of Singaporeans (1324 Chinese, 471 Malays and 375 Asian Indians) whose dietary fat intake was recorded by a validated questionnaire. When no stratification by fat intake was considered, the T allele was associated with higher plasma HDL-C concentrations (P = 0.001), higher triglyceride (TG) concentrations (P = 0.001) and higher HDL-C/TG ratios (P = 0.041). We found a highly significant interaction (P = 0.001) between polymorphism and fat intake in determining TG concentration and the HDL-C/TG ratio (P = 0.001) in the overall sample even after adjustment for potential confounders. Thus, TT subjects showed higher TG concentrations only when fat intake supplied >30% of total energy. This interaction was also found when fat intake was considered as continuous (P = 0.035). Moreover, in the upper tertile of fat intake, TT subjects had 45% more TG than CC individuals (P < 0.01). For HDL-C concentration, the gene-diet interaction was significant (P = 0.015) only in subjects of Indian origin. In conclusion, our results indicate that there are differences in the association of -514C>T polymorphism with plasma lipids according to dietary intake and ethnic background. Specifically, the TT genotype is associated with a more atherogenic lipid profile when subjects consume diets with a fat content > 30%.

[1]  S. Deeb,et al.  Hepatic lipase: a marker for cardiovascular disease risk and response to therapy , 2003, Current opinion in lipidology.

[2]  S. Kersten,et al.  Nutrigenomics: goals and strategies , 2003, Nature Reviews Genetics.

[3]  X. Adiconis,et al.  The TaqIB and −629C>A polymorphisms at the cholesteryl ester transfer protein locus: associations with lipid levels in a multiethnic population. The 1998 Singapore National Health Survey , 2002, Clinical genetics.

[4]  P. Raskin,et al.  Report of the expert committee on the diagnosis and classification of diabetes mellitus. , 1999, Diabetes care.

[5]  K. Chia,et al.  Ethnic differences in acute myocardial infarction in Singapore. , 2003, European heart journal.

[6]  J. Després,et al.  Visceral obesity attenuates the effect of the hepatic lipase -514C>T polymorphism on plasma HDL-cholesterol levels in French-Canadian men. , 2003, Molecular genetics and metabolism.

[7]  Jianfeng Xu,et al.  Positive results in association studies are associated with departure from Hardy-Weinberg equilibrium: hint for genotyping error? , 2002, Human Genetics.

[8]  P. Wilson,et al.  Dietary Fat Intake Determines the Effect of a Common Polymorphism in the Hepatic Lipase Gene Promoter on High-Density Lipoprotein Metabolism: Evidence of a Strong Dose Effect in This Gene-Nutrient Interaction in the Framingham Study , 2002, Circulation.

[9]  S. Nishtar.  Prevention of coronary heart disease in south Asia , 2002, The Lancet.

[10]  Y. Jang,et al.  Regulation of small dense LDL concentration in Korean and Scottish men and women. , 2002, Atherosclerosis.

[11]  E. Sijbrands,et al.  Hepatic lipase: a pro- or anti-atherogenic protein? , 2002, Journal of lipid research.

[12]  L. Martinez,et al.  Hepatic lipase: structure/function relationship, synthesis, and regulation. , 2002, Journal of lipid research.

[13]  T. Arinami,et al.  Relation of the -514C/T polymorphism in the hepatic lipase gene to serum HDL and LDL cholesterol levels in postmenopausal women under hormone replacement therapy. , 2002, Atherosclerosis.

[14]  Jonathan C. Cohen,et al.  Sources of variability in genetic association studies: Insights from the analysis of hepatic lipase (LIPC) , 2002, Human mutation.

[15]  D. Fang,et al.  Polymorphism of HL +1075C, but not -480T, is associated with plasma high density lipoprotein cholesterol and apolipoprotein AI in men of a Chinese population. , 2002, Atherosclerosis.

[16]  J. Hokanson,et al.  A common promoter polymorphism in the hepatic lipase gene (LIPC-480C>T) is associated with an increase in coronary calcification in type 1 diabetes. , 2002, Diabetes.

[17]  J. Ordovás.  Gene-diet interaction and plasma lipid response to dietary intervention , 2001, Biochemical Society transactions.

[18]  J. Schneider,et al.  Low Hepatic Lipase Activity Is a Novel Risk Factor for Coronary Artery Disease , 2001, Circulation.

[19]  N. Makridakis,et al.  Multiplex automated primer extension analysis: simultaneous genotyping of several polymorphisms. , 2001, BioTechniques.

[20]  K. Hughes,et al.  Risk factors and incident coronary heart disease in Chinese, Malay and Asian Indian males: the Singapore Cardiovascular Cohort Study. , 2001, International journal of epidemiology.

[21]  S. Humphries,et al.  Age-related effects of genetic variation on lipid levels: The Columbia University BioMarkers Study. , 2001, Pediatrics.

[22]  K. Tan,et al.  Effects of gender, hepatic lipase gene polymorphism and type 2 diabetes mellitus on hepatic lipase activity in Chinese. , 2001, Atherosclerosis.

[23]  H. Mabuchi,et al.  Effects of hepatic lipase gene promoter nucleotide variations on serum HDL cholesterol concentration in the general Japanese population , 2001, Journal of Human Genetics.

[24]  E. Tai,et al.  Diabetes mellitus abolishes ethnic differences in cardiovascular risk factors: lessons from a multi-ethnic population. , 2001, Atherosclerosis.

[25]  A. Verhoeven,et al.  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. , 2001, Atherosclerosis.

[26]  P. Deurenberg,et al.  Can dietary factors explain differences in serum cholesterol profiles among different ethnic groups (Chinese, Malays and Indians) in Singapore? , 2001, Asia Pacific journal of clinical nutrition.

[27]  S. Juo,et al.  Promoter polymorphisms of hepatic lipase gene influence HDL(2) but not HDL(3) in African American men: CARDIA study. , 2001, Journal of lipid research.

[28]  B. Zinman,et al.  Variable association between genetic variation in the CYP7 gene promoter and plasma lipoproteins in three Canadian populations. , 1999, Atherosclerosis.

[29]  S. Chew,et al.  Levels of cardiovascular disease risk factors in Singapore following a national intervention programme. , 2001, Bulletin of the World Health Organization.

[30]  P. Deurenberg,et al.  Validation of a semiquantitative food frequency questionnaire for estimation of intakes of energy, fats and cholesterol among Singaporeans. , 2000, Asia Pacific journal of clinical nutrition.

[31]  I. Vauhkonen,et al.  G-250A substitution in promoter of hepatic lipase gene is associated with dyslipidemia and insulin resistance in healthy control subjects and in members of families with familial combined hyperlipidemia. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[32]  S. Hong,et al.  Genetic variations of the hepatic lipase gene in Korean patients with coronary artery disease. , 2000, Clinical biochemistry.

[33]  T. Thuren.  Hepatic lipase and HDL metabolism. , 2000, Current opinion in lipidology.

[34]  P. Wilson,et al.  Association of the C-514T polymorphism in the hepatic lipase gene with variations in lipoprotein subclass profiles: The Framingham Offspring Study. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[35]  K. Hughes,et al.  Incidence of ischaemic heart disease and stroke in Chinese, Malays and Indians in Singapore: Singapore Cardiovascular Cohort Study. , 2000, Annals of the Academy of Medicine, Singapore.

[36]  G. Assmann,et al.  Treatment of hypertriglyceridemia by two diets rich either in unsaturated fatty acids or in carbohydrates: effects on lipoprotein subclasses, lipolytic enzymes, lipid transfer proteins, insulin and leptin , 2000, International Journal of Obesity.

[37]  S. Deeb,et al.  The C-514T polymorphism in the human hepatic lipase gene promoter diminishes its activity. , 2000, Journal of lipid research.

[38]  M. Lefevre,et al.  HDL-subpopulation patterns in response to reductions in dietary total and saturated fat intakes in healthy subjects. , 1999, The American journal of clinical nutrition.

[39]  J. Hokanson,et al.  A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[40]  E. Kass,et al.  Metabolic and genetic determinants of HDL metabolism and hepatic lipase activity in normolipidemic females. , 1999, Journal of lipid research.

[41]  S. Grundy,et al.  Hepatic lipase: new insights from genetic and metabolic studies. , 1999, Current opinion in lipidology.

[42]  E. Tai,et al.  Isolated low HDL cholesterol: an insulin-resistant state only in the presence of fasting hypertriglyceridemia. , 1999, Diabetes.

[43]  R. Krauss,et al.  A very low-fat diet is not associated with improved lipoprotein profiles in men with a predominance of large, low-density lipoproteins. , 1999, The American journal of clinical nutrition.

[44]  S. Emmanuel,et al.  Prevalence of diabetes and ethnic differences in cardiovascular risk factors. The 1992 Singapore National Health Survey. , 1999, Diabetes care.

[45]  P. Talmud,et al.  The T allele of the hepatic lipase promoter variant C-480T is associated with increased fasting lipids and HDL and increased preprandial and postprandial LpCIII:B : European Atherosclerosis Research Study (EARS) II. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[46]  J. Hokanson,et al.  Common variants in the promoter of the hepatic lipase gene are associated with lower levels of hepatic lipase activity, buoyant LDL, and higher HDL2 cholesterol. , 1998, Arteriosclerosis, thrombosis, and vascular biology.

[47]  Carol Ewing Garber,et al.  ACSM Position Stand: The Recommended Quantity and Quality of Exercise for Developing and Maintaining Cardiorespiratory and Muscular Fitness, and Flexibility in Healthy Adults , 1998 .

[48]  R. Krauss,et al.  Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men. , 1998, The American journal of clinical nutrition.

[49]  M. Taskinen,et al.  Association of variation in hepatic lipase activity with promoter variation in the hepatic lipase gene. The LOCAT Study Invsestigators. , 1998, The Journal of clinical investigation.

[50]  R. Hegele,et al.  Hepatic lipase deficiency. , 1998, Critical reviews in clinical laboratory sciences.

[51]  S. Grundy,et al.  Hepatic lipase activity is lower in African American men than in white American men: effects of 5' flanking polymorphism in the hepatic lipase gene (LIPC). , 1998, Journal of lipid research.

[52]  J. Jukema,et al.  Common C-to-T substitution at position -480 of the hepatic lipase promoter associated with a lowered lipase activity in coronary artery disease patients. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[53]  A. Cooper.  Hepatic uptake of chylomicron remnants. , 1997, Journal of lipid research.

[54]  L. Tiret,et al.  Hepatic lipase gene polymorphisms influence plasma HDL levels. Results from Finnish EARS participants. European Atherosclerosis Research Study. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[55]  S. Grundy,et al.  A hepatic lipase (LIPC) allele associated with high plasma concentrations of high density lipoprotein cholesterol. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[56]  R. Krauss,et al.  Associations of hepatic and lipoprotein lipase activities with changes in dietary composition and low density lipoprotein subclasses. , 1995, Journal of lipid research.

[57]  S. Grundy,et al.  Variation at the hepatic lipase and apolipoprotein AI/CIII/AIV loci is a major cause of genetically determined variation in plasma HDL cholesterol levels. , 1994, The Journal of clinical investigation.