Association of endothelial lipase gene (LIPG) haplotypes with high-density lipoprotein cholesterol subfractions and apolipoprotein AI plasma levels in Japanese Americans.
The LIPG gene on chromosome 18 encodes for endothelial lipase, a member of the triglyceride lipase family. Mouse models suggest that variation in LIPG influences high-density lipoprotein (HDL) metabolism, but only limited data are available in humans. This study examined associations of LIPG haplotypes, comprising a single nucleotide polymorphism (SNP) in the promoter region (-384A>C), and a nonsynonymous SNP in exon 3 (Thr111Ile or 584C>T), with lipoprotein risk factors in 541 adult Japanese Americans. A marginal association was found between LIPG diplotypes and HDL cholesterol (p=0.045). Stronger associations were seen for HDL3 cholesterol (p=0.005) and Apolipoprotein AI plasma levels (p=0.002). After adjustment for age, gender, smoking and medications, individuals homozygous for the minor allele at both SNPs (*4 haplotype) had a more favorable risk factor profile, compared to other haplotype combinations. No relationship was seen for plasma triglyceride levels or low-density lipoprotein (LDL) size, but the homozygous *4 diplotype was also associated with lower Apolipoprotein B and LDL cholesterol levels (p=0.001 and 0.015, respectively). In conclusion, this community-based family study of Japanese Americans demonstrates that LIPG variants are associated with HDL related risk factors, and may play a role in susceptibility to cardiovascular disease in this population.
Hutter
Carolyn M
CM
Department of Epidemiology, Institute for Public Health Genetics, School of Public Health and Community Medicine, University of Washington, 1959 N.E. Pacific Avenue, Box 357236, Seattle, WA 98195, USA.
Austin
Melissa A
MA
Farin
Federico M
FM
Viernes
Hannah-Malia
HM
Edwards
Karen L
KL
Leonetti
Donna L
DL
McNeely
Marguerite J
MJ
Fujimoto
Wilfred Y
WY
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D016632:Apolipoprotein A-I / Q000097:blood*; D001213:Asian; D002318:Cardiovascular Diseases / Q000097:blood / Q000208:ethnology* / Q000235:genetics; D008076:Cholesterol, HDL / Q000097:blood*; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D008049:Lipase / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D012189:Retrospective Studies; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology
D016632:Apolipoprotein A-I; D008076:Cholesterol, HDL; D004247:DNA; C410382:LIPG protein, human; D008049:Lipase