LACK OF ASSOCIATION OF THE APOLIPOPROTEIN A-I-C-III-A-IV GENE XMNI AND SSTI POLYMORPHISMS AND OF THE LIPOPROTEIN-LIPASE GENE-MUTATIONS IN FAMILIAR COMBINED HYPERLIPOPROTEINEMIA IN FRENCH-CANADIAN SUBJECTS

Familial combined hyperlipoproteinemia (FCH) is a common familial lipo protein disorder characterized by elevated plasma cholesterol and trig lyceride levels with segregation in first-degree relatives. Most affec ted subjects with FCH have elevated plasma levels of apolipoprotein (a pe) B. The disorder results from oversecretion of hepatic apoB-contain ing lipoprotein particles. The genetic defect(s) are unknown. Previous work has suggested that genetic polymorphisms of the apoA-I gene and functional abnormalities of the lipoprotein lipase (LPL) gene are asso ciated with FCH. We investigated the XmnI and SstI restriction fragmen t length polymorphisms (RFLP) of the apoA-I gene in FCH subjects of Fr ench Canadian descent. We also investigated three common functional mu tations of the lipoprotein lipase (LPL) gene (LPLgly188Glu, LPLPro207L eu, and LPLAsp(250)Asn) in French Canadians that account for approxima tely 97% of cases of complete LPL deficiency in the province of Quebec , Canada. We identified and characterized 54 FCH probands in lipid cli nics and examined at least one first-degree relative. There were 37 me n and 17 women (mean age 48 +/- 9 and 58 +/- 8 years, respectively). N one of the probands had diabetes mellitus; mean plasma glucose was 5.5 mmol/L. High blood pressure was diagnosed in 32% of men and 29% of wo men. The body mass index (weight (kg)/height(m(2))) was elevated in pr obands (27 +/- 4 for men and 26 +/- 4 for women). Mean plasma levels o f cholesterol (C) was 7.6 +/- 1.5 mmol/L, triglycerides 3.5 +/- 1.6 mm ol/L, LDL-C 4.9 +/- 1.2 mmol/L, HDL-C 1.0 +/- 0.3 mmol/L, and apoB 1.8 3 +/- 0.67 g/L in the probands. Allele frequency of the rare alleles o f the XmnI and SstI RFLP was not significantly different from a health y refer ence group. In several families studied, the XmnI and SstI RFL P did not unequivocally segregate with the FCH phenotype. There was no significant effect of the presence or absence of the XmnI or SstI RFL P's on plasma lipids, lipoprotein cholesterol or apoB levels. Only one FCH proband was found to have a mutation of the LPL gene ((Gly188Glu) ) and this did not segregate with the FCH phenotype in the family. We conclude that in our highly selected group of FCH subjects of French Canadian descent, the XmnI and SstI RFLPs of the apoA-I gene and commo n functional mutations of the LPL gene resulting in complete LPL defic iency are not associated with FCH.