Article

Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans.

Cardiology Division, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Nature Genetics (Impact Factor: 29.65). 02/2008; 40(2):189-97. DOI: 10.1038/ng.75
Source: PubMed

ABSTRACT Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.

0 Bookmarks
 · 
122 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: This study sought to investigate the correlation between the single nucleotide polymorphism (SNP) rs9958947C>T in the endothelial lipase (LIPG) gene promoter and lacunar infarction in the Han population in China. A case-control method was applied in this study, which included 378 patients with lacunar infarction in the patient group and 404 healthy individuals who received a routine physical examination in the control group. The polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were used to detect the SNP (rs9958947) in the LIPG promoter for the two groups. The T allele frequency (51.32%) and CT+TT genotype frequency (77.78%) in the patient group were significantly higher than those in the control group (43.32% and 66.34%, respectively). Comparison of the T allele frequency and CT+TT genotype frequency between the two groups showed statistically significant differences. Logistic regression analysis showed that the T allele, male, smoking, hypertension, hyperlipidemia and diabetes were independent risk factors for lacunar infarction in the Han population in China. Therefore, we concluded that SNP rs9958947 in the LIPG gene promoter is associated with the incidence of lacunar infarction.
    International Journal of Clinical and Experimental Medicine 01/2014; 7(11):4427-33. · 1.42 Impact Factor
  • Genetics and molecular research: GMR 01/2014; 13(2):3329-3336. · 0.85 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The role of triglyceride metabolism in different diseases, such as cardiovascular or cerebrovascular diseases is still under extensive investigations. In genome-wide studies several polymorphisms have been reported, which are highly associated with plasma lipid level changes. Our goal was to examine eight variants: rs12130333 at the ANGPTL3, rs16996148 at the CILP2, rs17321515 at the TRIB1, rs17145738 and rs3812316 of the MLXIPL, rs4846914 at GALNT2, rs1260326 and rs780094 residing at the GCKR loci. A total of 399 Roma (Gypsy) and 404 Hungarian population samples were genotyped using PCR-RFLP method. Significant differences were found between Roma and Hungarian population samples in both MLXIPL variants (C allele frequency of rs17145738: 94.1% vs. 85.6%, C allele frequency of rs3812316: 94.2% vs. 86.8% in Romas vs. in Hungarians, p Hungarians, p Hungarians, p SNPs could be verified and the known minor alleles showed no correlation with triglyceride levels in any population samples. The current study revealed fundamental differences of known triglyceride modifying SNPs in Roma population. Failure of finding evidence for affected triglyceride metabolism shows that these susceptibility genes are much less effective compared for example to the apolipoprotein A5 gene.
    Pathology & Oncology Research 01/2015; · 1.81 Impact Factor

Full-text (2 Sources)

Download
32 Downloads
Available from
Jun 1, 2014