Interaction effect of Serine447Stop variant of the lipoprotein lipase gene and C-514T variant of the hepatic lipase gene on serum triglyceride levels in young adults: the Bogalusa Heart Study.
The opposing effects of lipoprotein lipase (LPL) Serin447Stop (S447X) polymorphism and hepatic lipase (HL) C-514T polymorphism on serum triglyceride (TG) levels have been known. However, little is known about the interaction effect of these 2 functional gene variants on serum triglyceride levels. This aspect was examined in a community-based sample of 902 whites and 389 blacks aged 18 to 41 years, using a repeated measures analysis in a mixed model. The frequency of the LPL X447 allele was higher in whites than blacks (16% v 11%, P <.05); whereas the frequency of HL T-514 allele was higher in blacks than whites (77% v 40%, P <.001). The combined genotype distribution was also different between whites and blacks (P <.001). Although the frequency of carriers of both variants was similar in whites and blacks (7% v 8%), more whites carried the LPL X447 allele only (9% v 3%), and more blacks carried the HL T-514 allele only (70% v 33%). Mean levels of TG adjusted for age, sex, and body mass index (BMI) in carriers versus noncarriers of the LPL X447 allele were lower by 13.5% (P <.0001) in whites, 15.8% (P <.01) in blacks and 16.0% (P <.0001) in the total sample. No such phenotypic effect was noted with respect to HL T-514 allele either in blacks or whites, although the mean level in carriers was marginally (P =.08) higher in the total sample. The interaction effect of LPL and HL variants on TG levels was significant in the total sample (P =.016) and marginal in whites (P =.079). In the total sample, the decrease of TG in carriers versus noncarriers of the LPL X447 was 1.8-fold greater in carriers versus noncarriers of the HL T-514 allele (13.6 mg/dL v 7.4 mg/dL, P =.016). Whites tended to show a similar trend (16.8 mg/dL v 6.1 mg/dL, P =.079). Blacks also showed a similar, but nonsignificant, trend (10.4 mg/dL v 8.6 mg/dL, P =.45). These results by showing modulation of association between S447X variant of the LPL gene and serum TG by C-514T variant of the HL gene underscore the importance of gene-gene interactions in the assessment of genetic effects on complex traits.
Xin
Xue
X
Tulane Center for Cardiovascular Health, and Department of Epidemiology, Tulane School of Public Health and Tropical Medicine, New Orleans, LA 70112, USA.
Srinivasan
Sathanur R
SR
Chen
Wei
W
Boerwinkle
Eric
E
Berenson
Gerald S
GS
D000328:Adult; D000483:Alleles; D044383:Black People / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008071:Lipoprotein Lipase / Q000235:genetics*; D008099:Liver / Q000201:enzymology*; D008145:Louisiana; D008297:Male; D011110:Polymorphism, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood*; D044465:White People / Q000235:genetics*; D001741:Black or African American
D014280:Triglycerides; D008071:Lipoprotein Lipase