The interactive effects of hepatic lipase gene promoter polymorphisms with sex and obesity on high-density-lipoprotein cholesterol levels in Taiwanese-Chinese.
OBJECTIVE
Hepatic lipase (HL) is involved in the metabolism of several lipoproteins and plays a key role in reverse cholesterol transport. The aim of the current study was to test the statistical association between two HL gene promoter polymorphisms (HL-514C/T and HL-250G/A) and lipoprotein profiles in a Taiwanese-Chinese population.


METHODS
A sample population of 716 Taiwanese-Chinese individuals was analyzed. DNA was extracted from the blood and genotypes were determined by polymerase chain reaction, restriction enzyme digestion, and agarose gel electrophoresis.


RESULTS
Analysis of the data revealed that these two polymorphisms are in strong linkage disequilibrium (D/D(max)=0.97, P<0.001). A significantly lower total cholesterol/HDL-C ratio was noted for carriers with the -514T and -250A alleles compared to non-carriers (P=0.007 and 0.004, respectively). A significant trend of the association was also found on the high levels of high-density-lipoprotein cholesterol (HDL-C) among carriers with the -514T and -250A alleles as opposed to that of non-carriers (P=0.030 and 0.023, respectively). Multivariate analysis has demonstrated that the effects of HL-514C/T and HL-250G/A polymorphisms on HDL-C levels were not affected by subjects' sex, body mass index, plasma triglyceride levels and the cholesterol ester transfer protein gene TaqIB polymorphism. Subgroup analysis on each sex has revealed that the two studied polymorphisms were significantly associated with HDL-C levels among males but not significant in women. The same association between obese and non-obese men was not consistent. The P-value of the respective polymorphisms on HDL-C levels were 0.012 and 0.002 among obese men, but not significant among non-obese men.


CONCLUSIONS
Analysis of our data revealed an independent association between the HL gene promoter polymorphisms and HDL-C levels in Taiwanese-Chinese. The data also suggests that the HL-514C/T and HL-250G/A polymorphisms interact with sex and obesity on HDL-C levels. The findings give clues for identifying high risk population in preventive medicine and clinical diagnosis. The subsequent impacts on treatment profiles and prognosis were derived from this study.
Ko
Yu-Lin
YL
The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, No.199 Tung-Hwa North Road, Taipei, Taiwan, ROC. koyulin@adm.cgmh.org.tw
Hsu
Lung-An
LA
Hsu
Kuang-Hung
KH
Ko
Yu-Hsien
YH
Lee
Ying-Shiung
YS
D044466:Asian People / Q000235:genetics; D015992:Body Mass Index; D002352:Carrier Proteins / Q000235:genetics; D002784:Cholesterol / Q000097:blood; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D004587:Electrophoresis, Agar Gel; D005260:Female; D008040:Genetic Linkage; D006023:Glycoproteins; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012737:Sex Factors; D013624:Taiwan; D014280:Triglycerides / Q000097:blood
C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D006023:Glycoproteins; D014280:Triglycerides; D002784:Cholesterol; D008049:Lipase