INTERACTION OF THE LIPOPROTEIN-LIPASE ASPARAGINE-291-]SERINE MUTATIONWITH BODY-MASS INDEX DETERMINES ELEVATED PLASMA TRIACYLGLYCEROL CONCENTRATIONS - A STUDY IN HYPERLIPIDEMIC SUBJECTS, MYOCARDIAL-INFARCTION SURVIVORS, AND HEALTHY-ADULTS

A mutation in the lipoprotein lipase (LPL) gene, resulting in the subs titution of asparagine by serine at residue 291 (LPL-S291), was found to occur in young survivors of a myocardial infarction from Sweden, co mbined hyperlipidemic subjects from the United Kingdom, and type III h yperlipidemic subjects from Germany at allelic carrier frequencies no different from those found in companion healthy control subjects (3.63 vs. 3.37; 1.85 vs. 1.60; and 2.00 vs. 1.56%, respectively). In a grou p of 620 healthy middle-aged men from the United Kingdom with baseline and three subsequent annual lipid measurements, mean plasma triacylgl ycerol (TG), (but not plasma cholesterol) concentrations in carriers o f the mutation were significantly elevated over noncarriers (1.95 vs. 1.61 mmol/l, P = 0.05, and 5.83 vs. 5.65 mmol/l, P = 0.29, respectivel y). When these healthy control subjects were divided according to tert iles of body mass index (BMI), as expected, non-carriers whose BMI was in the upper two tertiles (BMI greater than or equal to 25.0 kg/m(2)) had higher plasma TG concentrations than those in the lowest tertile (1.90 vs. 1.54 mmol/l), but this difference was much greater in LPL-S2 91 carriers (2.33 vs. 1.36 mmol/l, P = 0.01, BMI x genotype interactio n, P = 0.02). To confirm this effect, a second group of 319 healthy su bjects from the United Kingdom was screened for LPL-S291. The allelic frequency of the mutation was found to be 1.88% and the effect on plas ma lipid concentrations was very similar to that observed in the first control group (plasma TG, 2.31 vs. 1.27 mmol/l, P < 0.001 for LPL-S29 1 carriers vs. non-carriers, respectively). As before, those carriers whose BMI was in the top two tertiles for this sample (BMI greater tha n or equal to 23.3 kg/m(2)) had higher plasma TG concentrations than n on-carriers (2.31 vs. 1.42 mmol/l). Thus, the LPL-S291 variant may pre dispose individuals to elevated plasma TG concentrations under conditi ons such as increased BMI.