8302A/C and (TTA)n polymorphisms in the HMG‐CoA reductase gene may be associated with some plasma lipid metabolic phenotypes in patients with coronary heart disease

Yu, Tong; Zhang, Sizhong; Hai, Li; Su, Zhiguang; Kong, Xiangdong; Liu, Hekun; Xiao, Cuiying; Sun, Yan; Shi, Jia

doi:10.1007/s11745-004-1225-3

Cited by 10 publications

(11 citation statements)

References 15 publications

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“…In HA, this is the first association data that showed significant associations between HMGCR haplotypes with multiple lipid/lipoprotein traits, especially with TG, s-LDL, and HDL-c. In CHA, we did not observe any association, although an association between 8302A/C variation of the HMGCR gene and lipids was reported in one Chinese study [33]. It should be noticed that the absence of H2 in CHA and the lack of the distinct, separable H4 and H8 haplotypes in AA and EA could well have accounted for the ethnic differences in the associations.…”

Section: Discussioncontrasting

confidence: 74%

The HMG‐CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi‐Ethnic Study of Atherosclerosis

Chen

Chen²,

Li³

et al. 2009

Lipids

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HMG-CoA reductase (HMGCR) is an enzyme involved in cholesterol synthesis. To investigate the contribution of the HMGCR gene to lipids and lipoprotein subfraction in different ethnicities, we performed an association study in the Multi-Ethnic Study of Atherosclerosis (MESA). Totally, 2444 MESA subjects (597 African-Americans (AA), 627 Chinese-Americans (CHA), 612 EuropeanAmericans (EA), and 608 Hispanic-Americans (HA)) without statin use were included. Participants had measurements of blood pressure, anthropometry, and fasting blood samples. Subjects were genotyped for 10 single nucleotide polymorphisms (SNPs). After excluding SNPs with minor allele frequency <5%, a single block was constructed. The most frequent haplotype was H1 (41-56%) in all ethnic groups except AA (H2a, 44.9%). Lower triglyceride level was associated with the H2a haplotype in AA and H2 in HA. In HA, H4 carriers had higher levels of triglyceride and small lowdensity lipoprotein (s-LDL), and lower high-density lipoprotein cholesterol (HDL-c), while carriers with H7 or H8 had associations with these traits in the opposite direction. No significant association was discovered in both CHA and EA. The total variation for triglyceride that could be explained by H2 alone was 2.6% in HA and 1.4% in AA. In conclusion, HMGCR gene variation is associated with multiple lipid/lipoprotein traits, especially with triglyceride, s-LDL, and HDL-c. The impact of the genetic variance is modest and differs greatly between ethnicities.

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Section: Discussioncontrasting

confidence: 74%

The HMG‐CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi‐Ethnic Study of Atherosclerosis

Chen

Chen²,

Li³

et al. 2009

Lipids

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“…C) was segregating in commercial pig breeds (Table 3) and showed significant whole-population associations, although at nominal level, with gluteus medius IMF content and serum TG at 45 days of age (Table 4). Similar effects have been described in humans, where analyses of an 830A/C polymorphism in human HMGCR gene resulted in higher levels of circulating low-density lipoprotein and TG in patients with the AA genotype (Tong et al, 2004). Considering the correction for multiple testing, the association tests with LDL-bound cholesterol reached the significance at experiment-wide level (P , 0.006) in family 3 (45 days) and family 5 (190 days), and also with TC in family 3 (45 days).…”

Section: Discussionsupporting

confidence: 69%

“…Expression of this gene represses the expression of low-density lipoprotein (LDL) receptors in liver, altering the serum cholesterol levels (reviewed in Kajinami et al, 2004). In agreement with this, polymorphisms on the human HMGCR gene have been associated with changes in the plasma cholesterol and triglyceride (TG) levels (Tong et al, 2004). Also, mutations resulting in alternative splicing of human exon 13 are a source of serum LDL-cholesterol variation (Burkhardt et al, 2008).…”

Section: Introductionmentioning

confidence: 91%

Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Cánovas

Quintanilla

Gallardo

et al. 2010

Animal

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The 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) is the rate-limiting enzyme in the biosynthesis of cholesterol. We have studied the role of theHMGCRgene in pig lipid metabolism by means of expression and structural analysis. We describe here the complete coding region of this gene in pigs and report two synonymous single nucleotide polymorphisms in the coding region. We have, additionally, studied the association of one of these polymorphisms (HMGCR:c.807A>C) with several lipid deposition- and cholesterol-related traits in a half-sib population generated from a commercial Duroc line, showing in some families a positive relationship ofHMGCR:c.807Aallele with serum low-density lipoprotein (LDL)-bound cholesterol and triglyceride levels, and also with intramuscular fat (IMF) content ofgluteus mediusmuscle. We have also assessed the expression levels in muscle and in liver from 68 Duroc individuals corresponding to the most extreme animals for the analysed traits. LiverHMGCRexpression correlated negatively with the serum high-density lipoprotein (HDL) levels, carcass lean percentage and stearic acid content, while muscle expression correlated also negatively with the carcass lean percentage, stearic and linoleic acids content, but showed a positive correlation with the serum lipid cholesterol (HDL, LDL and total cholesterol), IMF and muscle oleic and palmitic fatty acid content. With this information, we have performed an association analysis of expression data with lipid metabolism phenotypic levels and theHMGCRgenotype. The results indicate thatHMGCRexpression levels in muscle are different in the two groups of pigs with extreme values for fat deposition and total cholesterol levels, and also between animals with the differentHMGCRgenotypes.

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“…HMG-CoA reductase (HMGCR), a rate-limiting enzyme in cholesterol biosynthesis, is located under our linkage peak (Table 6). Polymorphisms in HMGCR may be associated with plasma lipid levels (75). Further studies will be needed to determine whether the QTL for TC that we found on 8p23 in the total family sample is distinct from our QTL for TG located ‫03ف‬ cM away.…”

Section: Discussionmentioning

confidence: 63%

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia

Wyszynski

Waterworth

et al. 2005

Journal of Lipid Research

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We conducted a genome-wide scan using variance components linkage analysis to localize quantitative-trait loci (QTLs) influencing triglyceride (TG), high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol, and total cholesterol (TC) levels in 3,071 subjects from 459 families with atherogenic dyslipidemia. The most significant evidence for linkage to TG levels was found in a subset of Turkish families at 11q22 [logarithm of the odds ratio (LOD) ‫؍‬ 3.34] and at 17q12 (LOD ‫؍‬ 3.44). We performed sequential oligogenic linkage analysis to examine whether multiple QTLs jointly influence TG levels in the Turkish families. These analyses revealed loci at 20q13 that showed strong epistatic effects with 11q22 (conditional LOD ‫؍‬ 3.15) and at 7q36 that showed strong epistatic effects with 17q12 (conditional LOD ‫؍‬ 3.21). We also found linkage on the 8p21 region for TG in the entire group of families (LOD ‫؍‬ 3.08). For HDL-C levels, evidence of linkage was identified on chromosome 15 in the Turkish families (LOD ‫؍‬ 3.05) and on chromosome 5 in the entire group of families (LOD ‫؍‬ 2.83). Linkage to QTLs for TC was found at 8p23 in the entire group of families (LOD ‫؍‬ 4.05) and at 5q13 in a subset of Turkish and Mediterranean families (LOD ‫؍‬ 3.72). These QTLs provide important clues for the further investigation of genes responsible for these complex lipid phenotypes. These data also indicate that a large proportion of the variance of TG levels in the Turkish population is explained by the interaction of multiple genetic loci.

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8302A/C and (TTA)n polymorphisms in the HMG‐CoA reductase gene may be associated with some plasma lipid metabolic phenotypes in patients with coronary heart disease

Cited by 10 publications

References 15 publications

The HMG‐CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi‐Ethnic Study of Atherosclerosis

The HMG‐CoA Reductase Gene and Lipid and Lipoprotein Levels: the Multi‐Ethnic Study of Atherosclerosis

Functional and association studies on the pig HMGCR gene, a cholesterol-synthesis limiting enzyme

Multiple QTLs influencing triglyceride and HDL and total cholesterol levels identified in families with atherogenic dyslipidemia

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