title: Multi-locus candidate gene analyses of lipid levels in a pediatric Turkish cohort: lessons learned on LPL, CETP, LIPC, ABCA1, and SHBG.
abstract: 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 (≤10th percentile) high density lipoprotein cholesterol (HDL-C) and high (≥90th 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.
authors.affiliation: 1 Department of Cardiology, Marmara University School of Medicine , Istanbul, Turkey .
authors.forename: Mehmet
authors.initials: M
authors.lastname: Agirbasli
authors.forename: Fatih
authors.initials: F
authors.lastname: Eren
authors.forename: Deniz
authors.initials: D
authors.lastname: Agirbasli
authors.forename: Marquitta J
authors.initials: MJ
authors.lastname: White
authors.forename: Scott M
authors.initials: SM
authors.lastname: Williams
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000235:genetics; D000293:Adolescent; D050197:Atherosclerosis / Q000097:blood* / Q000235:genetics; D002648:Child; D053480:Cholesterol Ester Transfer Proteins / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006801:Humans; D008049:Lipase / Q000235:genetics; D008055:Lipids / Q000097:blood*; D008071:Lipoprotein Lipase / Q000235:genetics; D008297:Male; D058885:Multilocus Sequence Typing; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000235:genetics; D014421:Turkey
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; C506642:CETP protein, human; D053480:Cholesterol Ester Transfer Proteins; C504173:LIPC protein, human; D008055:Lipids; D012738:Sex Hormone-Binding Globulin; D008049:Lipase; D008071:Lipoprotein Lipase