BACKGROUND: Dyslipidaemia, a key risk factor for cardiovascular disease (CVD), is strongly influenced by genetic factors. OBJECTIVE: To identify genetic factors affecting blood lipid concentrations and CVD risk factors in the Korean population by a candidate gene association analysis. METHODS: 21 single nucleotide polymorphisms (SNPs) that have been reported as associated with lipid concentrations in people of European ancestry were selected and their associations with CVD risk factors in Korean populations assessed. Genotype data from 7616 subjects without diabetes or lipid-lowering drugs were obtained from the Korean Association Resource (KARE) project. RESULTS: After adjustment for age and gender, five SNPs were identified that were associated with high-density lipoprotein-cholesterol (HDL-C; rs4420638: p=2.09×10⁻⁷), 11 SNPs with low-density lipoprotein-cholesterol (LDL-C; rs12654264: p=1.29×10⁻⁸) and eight SNPs with triglycerides (TG; rs4420638: p=1.80×10⁻⁶). Through analysis of multiple associations with lipid traits, after adjustment for age, gender, body mass index, smoking, alcohol consumption and hypertension, five SNPs (rs693, rs17321515, rs174547, rs688, rs4420638) were identified that were strongly associated with at least two of the following: HDL-C, LDL-C and TG. Of these, rs693, which lies in the APOB gene, was also significantly associated with the homoeostasis model assessment for insulin resistance (p=6.68×10⁻⁶) and γ-glutamyl transpeptidase (p=2.34×10⁻⁶), and rs174547, which lies in the FADS1 gene and was significantly associated with fasting plasma glucose (p=1.48×10⁻⁶). CONCLUSION: Several SNPs associated with lipid traits and CVD risk factors were identified. These findings may form the basis for further investigations to identify the causative polymorphisms in dyslipidaemia and CVD.
BACKGROUND: Dyslipidaemia, a key risk factor for cardiovascular disease (CVD), is strongly influenced by genetic factors. OBJECTIVE: To identify genetic factors affecting blood lipid concentrations and CVD risk factors in the Korean population by a candidate gene association analysis. METHODS: 21 single nucleotide polymorphisms (SNPs) that have been reported as associated with lipid concentrations in people of European ancestry were selected and their associations with CVD risk factors in Korean populations assessed. Genotype data from 7616 subjects without diabetes or lipid-lowering drugs were obtained from the Korean Association Resource (KARE) project. RESULTS: After adjustment for age and gender, five SNPs were identified that were associated with high-density lipoprotein-cholesterol (HDL-C; rs4420638: p=2.09×10⁻⁷), 11 SNPs with low-density lipoprotein-cholesterol (LDL-C; rs12654264: p=1.29×10⁻⁸) and eight SNPs with triglycerides (TG; rs4420638: p=1.80×10⁻⁶). Through analysis of multiple associations with lipid traits, after adjustment for age, gender, body mass index, smoking, alcohol consumption and hypertension, five SNPs (rs693, rs17321515, rs174547, rs688, rs4420638) were identified that were strongly associated with at least two of the following: HDL-C, LDL-C and TG. Of these, rs693, which lies in the APOB gene, was also significantly associated with the homoeostasis model assessment for insulin resistance (p=6.68×10⁻⁶) and γ-glutamyl transpeptidase (p=2.34×10⁻⁶), and rs174547, which lies in the FADS1 gene and was significantly associated with fasting plasma glucose (p=1.48×10⁻⁶). CONCLUSION: Several SNPs associated with lipid traits and CVD risk factors were identified. These findings may form the basis for further investigations to identify the causative polymorphisms in dyslipidaemia and CVD.
Authors: Zari Dastani; Marie-France Hivert; Nicholas Timpson; John R B Perry; Xin Yuan; Robert A Scott; Peter Henneman; Iris M Heid; Jorge R Kizer; Leo-Pekka Lyytikäinen; Christian Fuchsberger; Toshiko Tanaka; Andrew P Morris; Kerrin Small; Aaron Isaacs; Marian Beekman; Stefan Coassin; Kurt Lohman; Lu Qi; Stavroula Kanoni; James S Pankow; Hae-Won Uh; Ying Wu; Aurelian Bidulescu; Laura J Rasmussen-Torvik; Celia M T Greenwood; Martin Ladouceur; Jonna Grimsby; Alisa K Manning; Ching-Ti Liu; Jaspal Kooner; Vincent E Mooser; Peter Vollenweider; Karen A Kapur; John Chambers; Nicholas J Wareham; Claudia Langenberg; Rune Frants; Ko Willems-Vandijk; Ben A Oostra; Sara M Willems; Claudia Lamina; Thomas W Winkler; Bruce M Psaty; Russell P Tracy; Jennifer Brody; Ida Chen; Jorma Viikari; Mika Kähönen; Peter P Pramstaller; David M Evans; Beate St Pourcain; Naveed Sattar; Andrew R Wood; Stefania Bandinelli; Olga D Carlson; Josephine M Egan; Stefan Böhringer; Diana van Heemst; Lyudmyla Kedenko; Kati Kristiansson; Marja-Liisa Nuotio; Britt-Marie Loo; Tamara Harris; Melissa Garcia; Alka Kanaya; Margot Haun; Norman Klopp; H-Erich Wichmann; Panos Deloukas; Efi Katsareli; David J Couper; Bruce B Duncan; Margreet Kloppenburg; Linda S Adair; Judith B Borja; James G Wilson; Solomon Musani; Xiuqing Guo; Toby Johnson; Robert Semple; Tanya M Teslovich; Matthew A Allison; Susan Redline; Sarah G Buxbaum; Karen L Mohlke; Ingrid Meulenbelt; Christie M Ballantyne; George V Dedoussis; Frank B Hu; Yongmei Liu; Bernhard Paulweber; Timothy D Spector; P Eline Slagboom; Luigi Ferrucci; Antti Jula; Markus Perola; Olli Raitakari; Jose C Florez; Veikko Salomaa; Johan G Eriksson; Timothy M Frayling; Andrew A Hicks; Terho Lehtimäki; George Davey Smith; David S Siscovick; Florian Kronenberg; Cornelia van Duijn; Ruth J F Loos; Dawn M Waterworth; James B Meigs; Josee Dupuis; J Brent Richards; Benjamin F Voight; Laura J Scott; Valgerdur Steinthorsdottir; Christian Dina; Ryan P Welch; Eleftheria Zeggini; Cornelia Huth; Yurii S Aulchenko; 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