Association of hepatic lipase gene polymorphisms with hypertriglyceridemia and low high-density lipoprotein-cholesterol levels among South Indian subjects without diabetes.

AIM The aim of this study was to investigate the association of four variants of the hepatic lipase (HL [or LIPC]) gene with various lipid parameters among South Indian subjects with normal glucose tolerance (NGT). SUBJECTS AND METHODS In total, 747 NGT subjects were randomly selected from the Chennai Urban Rural Epidemiological Study (CURES). Serum triglycerides, serum cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured using a Hitachi-912 autoanalyzer (Roche Diagnostics GmbH, Mannheim, Germany). Genotyping of HL gene variants was done by the polymerase chain reaction-restriction fragment length polymorphism method, and 20% of samples were sequenced to validate the genotypes obtained. Haplotype analysis was also carried out. RESULTS The TT genotype of the rs1800588 C/T (C-480T) polymorphism was significantly associated with hypertriglyceridemia, with an adjusted odds ratio of 2.58 (95% confidence interval 1.38-4.85, P=0.003), whereas those with the CC genotype of the rs6074 A/C (Thr479Thr) had significantly lower HDL-C levels (41.3±9.8 mg/dL) compared with the AA genotype (43.6±10.2 mg/dL, P=0.02). Haplotype analysis showed the TGC haplotype was significantly associated with low HDL-C levels. CONCLUSIONS Among South Indian subjects without diabetes, the rs1800588 C/T (C-480T) and rs6074 C/A (Thr479Thr) variants of the HL gene are associated with hypertriglyceridemia and low HDL-C, respectively. The TGC haplotype was significantly associated with low HDL-C.

[1]  A. Shamshiri,et al.  Association between CETP Taq1B and LIPC -514C/T polymorphisms with the serum lipid levels in a group of Tehran's population: a cross sectional study , 2010, Lipids in Health and Disease.

[2]  David W. Williamson,et al.  Polymorphisms in the hepatic lipase gene affect plasma HDL-cholesterol levels in a Turkish population[S] , 2010, Journal of Lipid Research.

[3]  V. Mohan,et al.  Epidemiology of Cardiovascular Disease in Type 2 Diabetes: The Indian Scenario , 2010, Journal of diabetes science and technology.

[4]  T. Lehtimäki,et al.  Hepatic lipase promoter C‐480T polymorphism is associated with serum lipids levels, but not subclinical atherosclerosis: The Cardiovascular Risk in Young Finns Study , 2009, Clinical genetics.

[5]  E. Steyerberg,et al.  Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes , 2009, European Journal of Human Genetics.

[6]  V. Mohan,et al.  Dietary carbohydrates, glycemic load and serum high-density lipoprotein cholesterol concentrations among South Indian adults , 2009, European Journal of Clinical Nutrition.

[7]  A. El-Sohemy,et al.  Interactions between hepatic lipase and apolipoprotein E gene polymorphisms affect serum lipid profiles of healthy Canadian adults. , 2008, Applied physiology, nutrition, and metabolism = Physiologie appliquee, nutrition et metabolisme.

[8]  V. Mohan,et al.  A novel association of a polymorphism in the first intron of adiponectin gene with type 2 diabetes, obesity and hypoadiponectinemia in Asian Indians , 2008, Human Genetics.

[9]  R. Hegele,et al.  Genetic determinants of plasma lipoproteins , 2007, Nature Clinical Practice Cardiovascular Medicine.

[10]  V. Mohan,et al.  Epidemiology of type 2 diabetes: Indian scenario. , 2007, The Indian journal of medical research.

[11]  J. Reich,et al.  Concordant Association of Lipid Gene Variation with a Combined HDL/LDL-Cholesterol Phenotype in Two European Populations , 2006, Human Heredity.

[12]  V. Mohan,et al.  Association of lipoprotein lipase Hind III and Ser 447 Ter polymorphisms with dyslipidemia in Asian Indians. , 2006, The American journal of cardiology.

[13]  V. Mohan,et al.  Peroxisome proliferator‐activated receptor‐γ co‐activator‐1α (PGC‐1α) gene polymorphisms and their relationship to Type 2 diabetes in Asian Indians , 2005, Diabetic medicine : a journal of the British Diabetic Association.

[14]  Y. Ouchi,et al.  Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000. , 2005, Journal of atherosclerosis and thrombosis.

[15]  M. Daly,et al.  Haploview: analysis and visualization of LD and haplotype maps , 2005, Bioinform..

[16]  J. Cleeman,et al.  Implications of Recent Clinical Trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines , 2004, Arteriosclerosis, thrombosis, and vascular biology.

[17]  V. Mohan,et al.  Risk factors for coronary artery disease in Indians. , 2004, The Journal of the Association of Physicians of India.

[18]  V. Mohan,et al.  The Chennai Urban Rural Epidemiology Study (CURES)--study design and methodology (urban component) (CURES-I). , 2003, The Journal of the Association of Physicians of India.

[19]  S. Deeb,et al.  Hepatic lipase and dyslipidemia: interactions among genetic variants, obesity, gender, and diet. , 2003, Journal of lipid research.

[20]  S. Joshi Metabolic syndrome--emerging clusters of the Indian phenotype. , 2003, The Journal of the Association of Physicians of India.

[21]  Seil Oh,et al.  Hepatic lipase C514T polymorphism and its relationship with plasma HDL-C levels and coronary artery disease in Koreans. , 2003, Journal of biochemistry and molecular biology.

[22]  V. Mohan,et al.  Socioeconomic status and dyslipidaemia in a South Indian population: the Chennai Urban Population Study (CUPS 11). , 2003, The National medical journal of India.

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

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

[25]  L. Wasserman,et al.  Genomic control, a new approach to genetic-based association studies. , 2001, Theoretical population biology.

[26]  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.

[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]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[29]  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.

[30]  J. Cigarroa,et al.  Hepatic lipase (LIPC) promoter polymorphism in men with coronary artery disease. Allele frequency and effects on hepatic lipase activity and plasma HDL-C concentrations. , 1999, Arteriosclerosis, thrombosis, and vascular biology.

[31]  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.

[32]  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.

[33]  D. Bhat,et al.  Fetal Growth and Glucose and Insulin Metabolism in Four‐year‐old Indian Children , 1995, Diabetic medicine : a journal of the British Diabetic Association.

[34]  P. McKeigue Coronary heart disease in Indians, Pakistanis, and Bangladeshis: aetiology and possibilities for prevention. , 1992, British heart journal.

[35]  L. Chan,et al.  Structure of the human hepatic triglyceride lipase gene. , 1989, Biochemistry.

[36]  V. Mohan,et al.  Serum immunoreactive insulin responses to a glucose load in Asian Indian and European Type 2 (non-insulin-dependent) diabetic patients and control subjects , 1986, Diabetologia.

[37]  H. Keen,et al.  The Southall Diabetes Survey: prevalence of known diabetes in Asians and Europeans. , 1985, British medical journal.

[38]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[39]  Rajeev Gupta,et al.  Lipids in Health and Disease , 2008 .

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

[41]  R. Hegele,et al.  Human hepatic lipase mutations and polymorphisms , 1992, Human mutation.