Cardiovascular risk factors and atherosclerosis precursors were examined in 365 Turkish children and adolescents. Study participants were recruited at five different state schools. We tested single and multi-locus effects of six polymorphisms from five candidate genes, chosen based on prior known association with lipid levels in adults, for association with low ( £ 10 th percentile) high density lipoprotein cholesterol (HDL-C) and high ( ‡ 90 th percentile) triglycerides (TG), and the related continuous outcomes. We observed an association between CETP variant rs708272 and low HDL-C (allelic p = 0.020, genotypic p = 0.046), which was supported by an independent analysis, PRAT (PRAT control p = 0.027). Sex-stratified logistic regression analysis showed that the B2 allele of rs708272 decreased odds of being in the lower tenth percentile of HDL-C measurements (OR = 0.36, p = 0.02) in girls; this direction of effect was also seen in boys but was not significant (OR = 0.64, p = 0.21). Logistic regression analysis also revealed that the T allele of rs6257 (SHBG) decreased odds of being in the top tenth percentile of TG measurements in boys (OR = 0.43, p = 0.03). Analysis of lipid levels as a continuous trait revealed a significant association between rs708272 (CETP) and LDL-C levels in males ( p = 0.02) with the B2B2 genotype group having the lowest mean LDL-C; the same direction of effect was also seen in females ( p = 0.05). An effect was also seen between rs708272 and HDL-C levels in girls ( p = 0.01), with the B2B2 genotype having the highest mean HDL-C levels. Multi-locus analysis, using quantitative multifactor dimensionality reduction (qMDR) identified the previously mentioned CETP variant as the best single locus model, and overall model, for predicting HDL-C levels in children. This study provides evidence for association between CETP and low HDL-C phenotype in children, but the results appear to be weaker in children than previous results in adults and may also be subject to gender effects.
These three genetic polymorphisms are susceptibility loci and genotypes of these genes are neither necessary nor sufficient for the coronary artery disease to occur, but coexistence of high-risk alleles may increase the severity of coronary artery disease.
Hyperlipidemia is a major risk factor for coronary artery disease (CAD). Lipoprotein lipase (LPL) is an important enzyme in lipoprotein metabolism. S447X polymorphism of the LPL gene has been implicated in the pathogenesis of CAD. Carriers of X447 allele were reported to have lower triglyceride and higher high-density lipoprotein cholesterol levels as well as a reduced risk of CAD. We hypothesized that S447X gene polymorphism might have a protective effect for CAD. A total of 178 subjects (mean age 42.97 ± 6.5 years) who underwent coronary angiography for clinical indications were included in the study. The patients had been referred for evaluation of chest pain and/or abnormal stress tests, and were selected consecutively. Gensini scores were used to assess the severity of CAD; 97 patients were diagnosed with angiographically proven CAD, and 81 subjects did not display significant CAD (≥ 70%) angiographically. Genotyping of LPL S447X polymorphism was performed by real-time polymerase chain reaction amplification and fluorescent probe melting point analysis on the light cycler. The minor allele frequencies of LPL 447X allele were 11.1% and 6.2% among subjects without CAD compared with CAD subjects (P = 0.081) and 447X allele had favorable effects on lipid levels among CAD patients; 447X homozygotes and heterozygotes displayed lower total cholesterol (171 ± 37 vs 208 ± 48 mg/dl, P = 0.02), lower triglycerides (121 ± 72 vs 184 ± 86 mg/dl, P = 0.02), lower low-density lipoprotein cholesterol (102 ± 27 vs 129 ± 39 mg/dl, P = 0.03). Gensini scores were significantly lower among the heterozygotes and homozygotes of LPL 447X allele than in the LPL S447 homozygotes (15 ± 23 vs 25 ± 30, P = 0.048). S447X polymorphism of LPL gene may have a protective role for the severity of CAD. The beneficial effects of S447X polymorphism of the LPL gene may be through its favorable effects on lipid levels.
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