Dataset Information

ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study.

ABSTRACT: We evaluated six estrogen receptor 1 (ESR1) polymorphisms for association with ten plasma lipid and apolipoprotein traits in 1,847 individuals (941 females and 906 males) in the multi-generation Rochester Family Heart Study using a generalized estimating equation approach. Apolipoprotein A-I (apoA-I), apoA-II, and HDL-cholesterol (HDL-C) were associated with exon 4 rs1801132 (Pro325Pro) genotype (P = 0.0044, P = 0.0048, and P = 0.0035, respectively). Positive correlation between levels of apoA-I, apoA-II, and HDL-C and the number of G alleles was observed in females (P = 0.0120, P = 0.0032, and P = 0.0030), but not males (P > 0.05). Because few studies have evaluated the effect of ESR1 gene polymorphisms on lipid traits in children, we also stratified our sample at the age of 15 years. There was evidence of association between intron 1 single-nucleotide polymorphisms rs9322331 and rs9340799 and apoC-II, and triglycerides (TGs) in youths 15 years and younger. In youths, evidence of association between rs9322331 and rs9340799 and apoC-II was stronger in males (P = 0.0036 and P = 0.0124) than in females (P > 0.05), whereas evidence of association with TG was stronger in females (P = 0.0030 and P = 0.0024) than in males (P > 0.05). These findings suggest that ESR1 variation plays an age- and sex-dependent role in determining plasma lipid and apolipoprotein levels.

SUBMITTER: Klos KL

PROVIDER: S-EPMC2637157 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature

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ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study.

Klos Kathy L E KL Boerwinkle Eric E Ferrell Robert E RE Turner Stephen T ST Morrison Alanna C AC

Journal of lipid research 20080430 8

We evaluated six estrogen receptor 1 (ESR1) polymorphisms for association with ten plasma lipid and apolipoprotein traits in 1,847 individuals (941 females and 906 males) in the multi-generation Rochester Family Heart Study using a generalized estimating equation approach. Apolipoprotein A-I (apoA-I), apoA-II, and HDL-cholesterol (HDL-C) were associated with exon 4 rs1801132 (Pro325Pro) genotype (P = 0.0044, P = 0.0048, and P = 0.0035, respectively). Positive correlation between levels of apoA-I ...[more]

PMID: 18450649

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Project description:BackgroundSchistosomiasis mansoni is a parasitic liver disease, which causes several metabolic disturbances. Here, we evaluate the influence of Apolipoprotein E (APOE) gene polymorphism, a known modulator of lipid metabolism, on plasma lipid levels in patients with hepatosplenic schistosomiasis.Methodology/principal findingsBlood samples were used for APOE genotyping and to measure total cholesterol (TC), LDL-C, HDL-C and triglycerides. Schistosomiasis patients had reduced TC, LDL-C and triglycerides (25%, 38% and 32% lower, respectively; P<0.0001) compared to control individuals, whereas HDL-C was increased (10% higher; P?=?0.0136). Frequency of the common alleles, ?2, ?3 and ?4, was similar (P?=?0.3568) between controls (n?=?108) and patients (n?=?84), implying that APOE genotype did not affect susceptibility to the advanced stage of schistosomiasis. Nevertheless, while patient TC and LDL-C levels were significantly reduced for each allele (except TC in ?2 patients), changes in HDL-C and triglycerides were noted only for the less common ?2 and ?4 alleles. The most striking finding, however, was that accepted regulation of plasma lipid levels by APOE genotype was disrupted by schistosomiasis. Thus, while ?2 controls had higher TC and LDL-C than ?3 carriers, these parameters were lower in ?2 versus ?3 patients. Similarly, the inverse relationship of TG levels in controls (?2>?3>?4) was absent in patients (?2 or ?4>?3), and the increase in HDL-C of ?2 or ?4 patients compared to ?3 patients was not seen in the control groups.Conclusion/significanceWe confirm that human schistosomiasis causes dyslipidemia and report for the first time that certain changes in plasma lipid and lipoprotein levels depend on APOE gene polymorphism. Importantly, we also concluded that S. mansoni disrupts the expected regulation of plasma lipids by the different ApoE isoforms. This finding suggests ways to identify new metabolic pathways affected by schistosomiasis and also potential molecular targets to treat associated morbidities.

Project description:This study aims to determine the association between the apolipoprotein C-I polymorphism and the longevity and genetic variants in ApoC-I that can influence the serum lipid levels in Bama. ApoC-I genotypes were determined by Taqman single nucleotide polymorphism (SNP) genotyping assays in 178 long-lived inhabitants (longevity group aged from 90 to 110 years), 147 healthy controls (Control 1 group aged from 40 to 79 years old) from Bama County, and 190 healthy controls (Control 2 group aged from 40 to 79 years old) from Nandan County without a family history of longevity. Statistical analysis was conducted using SPSS 16.0. All genotype distributions of rs584007 and rs4420638 were consistent with the Hardy-Weinberg equilibrium (p > 0.05). Significant differences were observed in the frequencies of the three genotypes (GG, AG, and AA) among the longevity and the two control groups (χ² = 11.238, p = 0.024) for rs584007. No significant differences were observed in the frequencies of the three genotypes (GG, AG, and AA) among the longevity and the two control groups (χ² = 4.587, p = 0.318) for rs4420638. The levels of total cholesterol (TC), triglycerides (TG), high-density lipoprotein-cholesterol (HDL-c), and low-density lipoprotein-cholesterol (LDL-c) were not different among the three genotypes of rs584007 in the three groups. The levels of HDL-c for GG, AG, and AA were significantly different (the highest being in the longevity group), while the levels of TG for AA and AG genotypes (the lowest being in the longevity group) and the levels of LDL-c for AG were significantly different (p < 0.05) among the three groups for rs584007. The levels of TG and HDL-c were significantly different among the three rs4420638 genotypes in the longevity group. The levels of TC for GG, AG, and AA were significantly different in the Control 2 group, while the levels of TG and HDL-c for AA and AG genotypes were significantly different (p < 0.05) among the three groups for rs4420638. The level of HDL-c was highest in the longevity group for AA and AG genotypes, and the level of TG was highest in the Control 2 group for rs4420638. Serum lipid parameters were related to environmental factors, including age, gender, BMI, DBP, SBP, rs4420638, and rs584007. The ApoC-I polymorphism might be one of the genetic factors of longevity in Bama. The ApoC-I rs4420638 and rs584007 SNPs are associated with serum TG and HDL-c levels in the longevous population.

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Dataset Information

ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study.

Publications

ESR1 polymorphism is associated with plasma lipid and apolipoprotein levels in Caucasians of the Rochester Family Heart Study.

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