The −250G→A polymorphism in the human hepatic lipase gene promoter affects blood lipids in Chinese

Zhao, Shui‐Ping; Xie, Xiang-Zhu; Nie, Shaoping

doi:10.1016/j.cca.2005.08.013

Cited by 14 publications

(16 citation statements)

References 19 publications

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“…According to our eQTL data, rs17231506 reduces the expression of CETP , in line with the observation that CETP deficiency or pharmacological inhibition leads to elevated serum HDL. Further, our eQTL data showed that rs2070895 (−250 G > A) increases the expression of LIPC and would be expected to be associated with decreased HDL blood 32 .…”

Section: Resultsmentioning

confidence: 74%

A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver

Strunz¹,

Graßmann²,

Gayán³

et al. 2018

Sci Rep

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Genome-wide association studies (GWAS) have identified numerous genetic variants in the human genome associated with diseases and traits. Nevertheless, for most loci the causative variant is still unknown. Expression quantitative trait loci (eQTL) in disease relevant tissues is an excellent approach to correlate genetic association with gene expression. While liver is the primary site of gene transcription for two pathways relevant to age-related macular degeneration (AMD), namely the complement system and cholesterol metabolism, we explored the contribution of AMD associated variants to modulate liver gene expression. We extracted publicly available data and computed the largest eQTL data set for liver tissue to date. Genotypes and expression data from all studies underwent rigorous quality control. Subsequently, Matrix eQTL was used to identify significant local eQTL. In total, liver samples from 588 individuals revealed 202,489 significant eQTL variants affecting 1,959 genes (Q-Value < 0.001). In addition, a further 101 independent eQTL signals were identified in 93 of the 1,959 eQTL genes. Importantly, our results independently reinforce the notion that high density lipoprotein metabolism plays a role in AMD pathogenesis. Taken together, our study generated a first comprehensive map reflecting the genetic regulatory landscape of gene expression in liver.

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Section: Resultsmentioning

confidence: 74%

A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver

Strunz¹,

Graßmann²,

Gayán³

et al. 2018

Sci Rep

View full text Add to dashboard Cite

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“…To date, there has been considerable evidence about -250 G/A variant and plasma lipoprotein concentrations, but the result remains inconsistent [52,102-104]. Influence of gender-specificity on the association was found in some studies [51,103,104]. Transgenic mice studies has demonstrated that overexpression of HL has led to a marked reduction in plasma HDL-C [105], however, there have existed many contradictory results in clinical epidemiological studies, which may be attributed to various factors, such as (i)restriction in terms of sample size and ethnic diversity; (ii)the integrated effects of multiple polymorphisms of genes, for instance, Wood KC et al indicated interactions during LIPC-514C/T and LIPC-250 G/A and apoE gene polymorphisms could distinctly influence serum lipid profiles [106]; (iii)both having pro-atherogenic and anti-atherogenetic properties for HL [107,108]; (iv)related to HDL subclasses, mainly as HDL 2 -C [49], etc.…”

Section: Discussionmentioning

confidence: 99%

Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease

et al. 2012

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ObjectivesAccumulating evidence suggested that dysregulation of cholesterol homeostasis might be a major etiologic factor in initiating and promoting neurodegeneration in Alzheimer’s disease (AD). ATP-binding cassette transporter A1 (ABCA1), hepatic lipase (HL, coding genes named LIPC) and cholesteryl ester transfer protein (CETP) are important components of high-density lipoprotein (HDL) metabolism and reverse cholesterol transport (RCT) implicated in atherosclerosis and neurodegenerative diseases. In the present study, we will investigate the possible association of several common polymorphisms (ABCA1R219K, CETPTaqIB and LIPC-250 G/A) with susceptibility to AD and plasma lipid levels.MethodsCase–control study of 208 Han Chinese (104 AD patients and 104 non-demented controls) from Changsha area in Hunan Province was performed using the PCR-RFLP analysis. Cognitive decline was assessed using Mini Mental State Examination (MMSE) as a standardized method. Additionally, fasting lipid profile and the cognitive testing scores including Wechsler Memory Scale (WMS) and Wisconsin Card Sorting Test (WCST) were recorded.Results and conclusionsWe found significant differences among the genotype distributions of these three genes in AD patients when compared with controls. But after adjusting other factors, multivariate logistic regression analysis showed only ABCA1R219K (B = −0.903, P = 0.005, OR = 0.405, 95%CI:0.217-0.758) and LIPC-250 G/A variants(B = −0.905, P = 0.018, OR = 0.405, 95%CI:0.191-0.858) were associated with decreased AD risk. There were significantly higher levels of high-density lipoprotein cholesterol (HDL-C) and apolipoproteinA-I in the carriers of KK genotype and K allele (P < 0.05), and B2B2 genotype of CETP Taq1B showed significant association with higher HDL-C levels than other genotypes (F = 5.598, P = 0.004), while -250 G/A polymorphisms had no significant effect on HDL-C. In total population, subjects carrying ABCA1219K allele or LIPC-250A allele obtained higher MMSE or WMS scores than non-carriers, however, no significant association was observed in AD group or controls. Therefore, this preliminary study showed that the gene variants of ABCA1R219K and LIPC-250 G/A might influence AD susceptibility in South Chinese Han population, but the polymorphism of CETPTaq1B didn't show any association in despite of being a significant determinant of HDL-C.

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“…[ 7 8 ] The Four common single nucleotide polymorphisms (SNPs) in the promoter region, consist of four highly correlated polymorphism in the 5’-Flanking region of the LIPC gene (-250 G/A,-514C/T,-710T/C and -763A/G) with respect to the transcription star site, were determined to be in perfect disequilibrium. [ 9 10 ] A substitution in the promoter region of the LIPC gene (-250G/A) has been reported to be related to modifications of plasma lipid levels[ 11 12 13 14 15 16 17 18 ] and the risk of CAD[ 19 20 ] in some studies but not in others. [ 21 22 23 24 ] In addition, this SNP of LIPC gene has been shown to regulate insulin sensitivity,[ 15 ] but its effect on the risk of CAD in type 2 diabetes has not been completely understood.…”

Section: Introductionmentioning

confidence: 99%

Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients

et al. 2016

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Background:Variations in the hepatic lipase (HL) gene are the potential candidate for coronary artery disease (CAD) especially in type 2 diabetes mellitus (T2DM) in diverse populations. We assessed the association of -514C/T and -250G/A polymorphisms in HL (LIPC) gene with CAD risk in Iranian population with type 2 diabetes.Materials and Methods:We evaluated 322 type 2 diabetic patients, 166 patients with normal angiograms as controls and 156 patients those identified with CAD undergoing their first coronary angiography as CAD cases. Genotyping of -514C/T and -250G/A polymorphisms in the promoter of the LIPC gene were studied by polymerase chain reaction (PCR)-restriction fragment length polymorphism technique.Results:Genotype distributions in CAD cases (73.7%, 20.5%, and 5.8% for −250G/A) and (62.2%, 32.7%, and 5.1% for -514C/T) were significantly different from those in controls (60.8%, 37.4%, and 1.8% for -250G/A) and (51.2%, 48.2%, and 0.6% for -514C/T). CAD cases had lower A-allele frequency than controls (0.131 vs. 0.196, P = 0.028). The odds ratio for the presence of -250 (GG + GA) genotype and A allele in CAD cases were 2.206 (95% confidence interval [CI] =1.33–3.65, P = 0.002) and 1.609 (95% CI = 1.051 −2.463, P = 0.029) respectively. Haplotype analysis demonstrated a significant association between especially LIPC double mutant (−250 A/-514 T) haplotype and presence of CAD.Conclusion:Our findings indicated that -250 G/A polymorphism rather than -514 C/T polymorphism of LIPC gene is more associated with the increased risk of CAD particularly in women with T2DM.

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The −250G→A polymorphism in the human hepatic lipase gene promoter affects blood lipids in Chinese

Cited by 14 publications

References 19 publications

A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver

A mega-analysis of expression quantitative trait loci (eQTL) provides insight into the regulatory architecture of gene expression variation in liver

Association studies of several cholesterol-related genes (ABCA1, CETP and LIPC) with serum lipids and risk of Alzheimer’s disease

Association between two common polymorphisms (single nucleotide polymorphism -250G/A and -514C/T) of the hepatic lipase gene and coronary artery disease in type 2 diabetic patients

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