title: Hepatic lipase gene -514 C/T polymorphism and premature coronary heart disease.
abstract: BACKGROUND
  A common polymorphism in the hepatic lipase (HL) gene promoter, -514C/T, affecting enzyme activity, has been associated with alterations in plasma lipoprotein levels. However a relationship with coronary heart disease (CHD) is less well documented.
  
  
  METHODS
  We studied HL -514 C/T in 562 Caucasian CHD patients aged under 50 years and in 642 Caucasian community recruited subjects without historical evidence of CHD.
  
  
  RESULTS
  Male CHD subjects (n = 490) had a 41% carrier rate for the C to T substitution, compared with 33% in corresponding controls (n = 330), [OR = 1.42 (95% CI:1.06-1.90), P < 0.02], T allele frequencies being 0.231 and 0.177 respectively [OR = 1.39 (1.08-1.78), P < 0.01]. In male CHD subjects, the T allele was associated with higher HDL-cholesterol (HDL-C) (CC: 0.95 +/- 0.24 (SD); CT: 1.04 +/- 0.41; TT: 1.01 +/- 0.20 mmol/l, P = 0.02, ANOVA) but the trend was not significant in females. In male CHD patients the T allele was more frequently encountered in those with high (> 4.5 mmol/l) than in those with low triglycerides [68% vs. 39%, OR = 3.13 (1.54-6.67), P = 0.001]. In community control subjects, the T allele was associated with a trend to higher HDL-C levels, the significance varying between subgroups while, in males, serum total and LDL-cholesterol were significantly lower in T homozygotes than in the other two genotypes (LDL-C: 2.73 +/- 0.63 vs. 3.56 +/- 0.95 mmol/l; P = 0.01). During the course of this study, a previously unreported promoter region polymorphism was found exclusively on -514C chromosomes (-592A/G, A allele frequency 0.108, 95% CI 0.09 - 0.126). It can lead to mistyping of C as T alleles in C/T heterozygotes, resulting in overestimation of -514 T homozygotes.
  
  
  CONCLUSIONS
  The T allele of the hepatic lipase -514 C/T polymorphism is associated with changes in plasma lipids. The superficially paradoxical predisposition to CHD in males is attributable to impairment of TG rich lipoprotein metabolism and reverse cholesterol transport.
authors: Cardiovascular Genetics Laboratory, Royal Perth Hospital, Department of Medicine, University of Western Australia and the Western Australian Heart Research Institute, Australia.
authors: Juying
authors: J
authors: Ji
authors: Carly E
authors: CE
authors: Herbison
authors: Cyril D S
authors: CD
authors: Mamotte
authors: Valerie
authors: V
authors: Burke
authors: Roger R
authors: RR
authors: Taylor
authors: Frank M
authors: FM
authors: van Bockxmeer
mesh_terms: D000328:Adult; D000367:Age Factors; D001315:Australia; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics; D003327:Coronary Disease / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D005838:Genotype; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D013997:Time Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides; D008049:Lipase