Abstract 21482: The Effect of Lecithin: Cholesterol Acyltransferase Genotypes, Enzyme Levels and Activity on High Density Lipoprotein Levels In Turkish Population
Lecithin: cholesterol acyltransferase (LCAT) is one of the key enzymes controlling the cholesterol homeostasis and transport and has a pivotal role in HDL maturation and remodeling. We evaluated the effects of 3 different genetic polymorphisms in LCAT gene (511C/T polymorphism (exon 4), 4886C/T (exon 6), 608C/T (exon 5)) on LCAT level and activity in subjects with low (<35 mg/dL) or high high density lipoprotein cholesterol (HDL-C) levels (>65 mg/dL).
Methods: Standard polymerase chain reaction protocols were followed by restriction enzyme digestions to genotype the subjects with high (>65 mg/dl) (n=50) or low HDL-C (<35 mg/dl) (n=50). LCAT activity was measured with a colorimetric enzymatic method. LCAT plasma level was measured by commercially available assay.
Results: 511C/T and 608C/T polymorphisms appeared to be a rare variants. On the other hand, 4886C/T polymorphism was commonly observed. Allele frequencies were in accordance with Hardy-Weinberg (HW) (K²<3.5). T allele frequencies in subjects with low (HDL<35 mg/dL) and high HDL-C (HDL>65 mg/dL) were 0.54 and 0.37 respectively (p=0.019). In subjects with low HDL-C, LCAT levels correlated positively with HDL-C levels (p=0.006, r=0.404), triglyceride levels (p=0.001, r=0.487), total cholesterol (p<0.001, r=0.541), LDL-C (p=0.001, r=0.477), body mass index (p<0.001, r=0.544). LCAT activity correlated positively with fasting glucose levels (p=0.008 r=0.390). No significant correlations were observed in the high HDL-C group. The 4886C/T genotype distribution among subjects with high and low HDL-C groups also displayed differences. TT genotype was more common among the low HDL-C group (30% vs 14%, p=0.05). In subjects with low HDL-C, mean HDL-C levels according to the genotypes were; CC 26±7, CT 29±5, TT 31±4 (p=0.05). No differences were noted between genotypes among the high HDL-C group.
Conclusion: The relation between HDL-C, LCAT enzyme level and function displays differences among low versus high HDL-C subjects. Small sized α4 and spherical α3 particles are the preferred substances for LCAT and the enzyme may be more instrumental in modulating HDL-C levels, function and cardiovascular risk among subjects with low HDL-C.
- © 2010 by American Heart Association, Inc.