Different Genes and Polymorphisms Affecting High-Density Lipoprotein Cholesterol Levels in Greek Familial Hypercholesterolemia Patients

Familial Hypercholesterolemia (FH) is a genetic disorder characterized by high low-density lipoprotein cholesterol (LDL-C) concentrations that frequently gives rise to premature coronary artery disease. The clinical expression of FH is highly variable, even in patients carrying the same LDL receptor gene mutation. This variability may be due to environmental and other genetic factors. We investigated the effect of APOCIII T1100C, FV Gln506Arg, ADRB2 Glu27Gln, SELE Ser128Arg, SELE Leu554Phe, and ENaCa Ala663Thr polymorphisms on the HDL-C variations in 84 patients with FH. For ApoCIII T1100C, subjects with the TT genotype presented higher HDL-C levels than the other genotype groups (p = 0.046). Similarly the presence of the Gln allele in ADRB2 27 Glu/Gln heterozygotes and ADRB2 27 Gln/Gln homozygotes was associated with higher HDL-C levels (p = 0.014). Among the other polymorphisms tested, none of them were associated with variations in HDL-C levels. The influence of each polymorphism on lipid concentrations was evaluated with linear regression analyses after adjustment for age and sex. Among the variables studied including total cholesterol, LDL-C, high-density lipoprotein (HDL)-C, triglycerides, apolipoprotein A (Apo-A) and B (Apo-B), and lipoprotein alpha (LP alpha), HDL-C concentration was significantly different in models applied for polymorphisms ApoCIII T1100C, FV Gln506Arg, and ADRB2 Glu27Gln (p = 0.01, p = 0.018, p = 0.04, respectively). These results suggest that HDL-C levels in FH heterozygotes may be affected by several different genetic variants.