Lipoprotein lipase mutations, plasma lipids and lipoproteins, and risk of ischemic heart disease - A meta-analysis

Background-We assessed in mete-analyses the effect of the Gly188Glu, Asp9As n, Asn291Ser, and Ser447Ter substitutions in lipoprotein lipase in the hete rozygous state on lipid metabolism and risk of ischemic heart disease (same order used below). Methods and Results-In 29 separate studies, 20 903 white subjects were scre ened for greater than or equal to 1 of these substitutions; each meta-analy sis included only some of these individuals. In population-based studies, h eterozygote frequencies ranged from 0.04% to 0.2%, 2% to 4%, 1% to 7%, and 17% to 22% for the respective substitutions. Postheparin plasma lipoprotein lipase activity decreased 53% (95% CI, 31% to 75%) (only 1 study), 30% (22 % to 37%), and 22% (8% to 35%) and was unchanged at 4% (-10% to 19%), respe ctively. Plasma triglycerides increased 78% (95% CI, 64%, to 92%), 20% (9% to 33%), and 31% (20% to 43%) and decreased 8% (4% to 11%), respectively. H DL cholesterol decreased 0.25 mmol/L (0.18 to 0.32), 0.08 mmol/L (0.04 to 0 .12), and 0.12 mmol/L (0.10 to 0.15) and increased 0.04 mmol/L (0.02 to 0.0 6), respectively. Odds ratios for ischemic heart disease were 4.9 (95% CI, 1.2 to 20) (only 1 study), 1.4 (0.8 to 2.4), 1.2 (0.9 to 1.5), and 0.8 (0.7 to 1.0), respectively. Subgroup analysis indicated that women with the Asn 291Ser substitution may have an increased risk of ischemic heart disease. Conclusions-These meta-analyses suggest that compared with noncarriers, car riers of the Gly188Glu, Asp9Asn, and Asn291Ser substitutions have an athero genic lipoprotein profile, whereas carriers of the Ser447Ter substitution h ave a protective lipoprotein profile. Accordingly, risk of ischemic heart d isease in heterozygous carriers is increased for Gly188Glu carriers; at mos t, the increase is borderline for Asp9Asn and Asn291Ser carriers; and risk is possibly decreased for Ser447Ter carriers.