Effect of gender on phenotypic expression of the S447X mutation in LPL: the Copenhagen City Heart Study.
The G188E, D9N, and N291S mutations in LPL increase TG, reduce HDL cholesterol, and increase risk of ischemic heart disease. The common S447X mutation may have opposite effects. We genotyped 8451 women and men from the Danish general population, and 854 women and men with ischemic heart disease. Participants carrying G188E, D9N, or N291S were excluded. Compared with non-carriers, female heterozygotes and homozygotes presented with a 0.11 and 0.18 mmol/l decrease in plasma TG (P=0.001 and P=0.37) and a 0.07 and 0.03 mmol/l increase in HDL cholesterol (P=0.001 and P=0.99). Male heterozygotes and homozygotes presented with a 0.20 and 0.41 mmol decrease in plasma TG (P<0.001 and P=0.06), which was twice that in women, and a 0.05 and 0.17 mmol/l increase in plasma HDL cholesterol (P=0.02 and P=0.04), respectively. In meta-analyses by gender, the S447X mutation was associated with a significant l7% reduction in risk of ischemic heart disease in men (OR=0.83; P=0.01), whereas risk was unaffected in women (OR=0.97; P=0.98). The S447X mutation is associated with anti-atherogenic effects on TG and HDL cholesterol in both genders, and with a moderate protective effect on risk of ischemic heart disease in men.
Department of Clinical Biochemistry, Herlev University Hospital, Copenhagen, Denmark.
Hans H
HH
Wittrup
Børge G
BG
Nordestgaard
Rolf
R
Steffensen
Gorm
G
Jensen
Anne
A
Tybjaerg-Hansen
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001054:Apolipoproteins A / Q000032:analysis / Q000235:genetics; D008076:Cholesterol, HDL / Q000032:analysis / Q000235:genetics; D015331:Cohort Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005786:Gene Expression Regulation; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006801:Humans; D008071:Lipoprotein Lipase / Q000032:analysis / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017202:Myocardial Ischemia / Q000453:epidemiology / Q000235:genetics*; D010641:Phenotype; D012494:Sampling Studies; D012737:Sex Factors; D018709:Statistics, Nonparametric; D014280:Triglycerides / Q000032:analysis / Q000235:genetics; D014505:Urban Population
D001054:Apolipoproteins A; D008076:Cholesterol, HDL; D014280:Triglycerides; D008071:Lipoprotein Lipase