TY - JOUR
T1 - Effect of gender on phenotypic expression of the S447X mutation in LPL
T2 - the Copenhagen City Heart Study
AU - Wittrup, Hans H
AU - Nordestgaard, Børge G
AU - Steffensen, Rolf
AU - Jensen, Gorm
AU - Tybjaerg-Hansen, Anne
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Adult
KW - Age Factors
KW - Aged
KW - Aged, 80 and over
KW - Analysis of Variance
KW - Apolipoproteins A/analysis
KW - Cholesterol, HDL/analysis
KW - Cohort Studies
KW - Denmark/epidemiology
KW - Female
KW - Gene Expression Regulation
KW - Gene Frequency
KW - Genetic Predisposition to Disease
KW - Heterozygote
KW - Humans
KW - Lipoprotein Lipase/analysis
KW - Logistic Models
KW - Male
KW - Middle Aged
KW - Mutation
KW - Myocardial Ischemia/epidemiology
KW - Phenotype
KW - Sampling Studies
KW - Sex Factors
KW - Statistics, Nonparametric
KW - Triglycerides/analysis
KW - Urban Population
U2 - 10.1016/s0021-9150(02)00183-1
DO - 10.1016/s0021-9150(02)00183-1
M3 - Journal article
C2 - 12208477
SN - 0021-9150
VL - 165
SP - 119
EP - 126
JO - Atherosclerosis
JF - Atherosclerosis
IS - 1
ER -