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. 2012 Nov;61(11):1523-7.
doi: 10.1016/j.metabol.2012.05.004. Epub 2012 Jun 26.

SNPs affecting serum metabolomic traits may regulate gene transcription and lipid accumulation in the liver

Snezana Mirkov  1 , Jamie L Myers, Jacqueline Ramírez, Wanqing Liu
Affiliations

SNPs affecting serum metabolomic traits may regulate gene transcription and lipid accumulation in the liver

Snezana Mirkov et al. Metabolism. 2012 Nov.

Abstract

Objective: Circulatory metabolites are important biomarkers for many diseases, especially metabolic disorders. The biological mechanism regulating circulatory levels of metabolites remains incompletely understood. Focusing on the liver as the central organ controlling metabolic homeostasis, we investigated the potential function of nine polymorphisms associated with serum metabolomic traits in a recent GWAS.

Materials/methods: The mRNA levels of the associated genes were measured by real-time PCR and correlated with genotypes in normal liver tissue (n=42). Genotype and mRNA data were also correlated with total hepatic lipid content (HLC). Our findings were also compared with the previously published gene expression quantitative traits loci (eQTL) data in the liver.

Results: We found that seven out of nine genes were highly expressed in hepatic tissue, while expression of four genes was significantly or marginally associated with genotypes (SPTLC3 vs rs168622, P=.002; ACADS vs rs2014355, P=.016; PLEKHH1 vs rs7156144, P=.076; ACADL vs rs2286963, P=.068). The SNP rs168622 at the SPTLC3 locus was also significantly correlated with HLC (P=.02). HLC was significantly correlated with FADS1 (r=-0.45; P=.003) and ETFDH (r=0.33; P=.037) expression. When compared with published eQTL data, SNPs in SPTLC3, ACADS, ELOVL2 and FADS1 were also in strong linkage disequilibrium (R(2)≥0.41, D'≥0.96) with eQTLs significantly affecting expression of these genes (P≤1.74×10(-5)).

Conclusions: Our study suggests that genetic variants affecting serum metabolites levels may play a functional role in the liver. This may help elucidate the mechanism by which genetic variants are involved in metabolic diseases.

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Figures

Figure 1
Figure 1. Correlations between SNPs, mRNA and hepatic lipid content (HLC) in liver tissue
A) rs168622 and SPTLC3; B) rs2014355 and ACADS; C) rs7156144 and PLEKHH1; D) rs2286963 and ACADL; E) FADS1 and HLC; F) ETFDH and HLC; and G) rs168622 and HLC. HLC and all gene expression data (ratio between each gene and the internal control TBP gene) were log transformed (+log10).
See this image and copyright information in PMC

References

    1. Illig T, Gieger C, Zhai G, et al. A genome-wide perspective of genetic variation in human metabolism. Nat Genet. 2010;42:137–141. - PMC - PubMed
    1. Li M, Song J, Mirkov S, et al. Comparing morphometric, biochemical, and visual measurements of macrovesicular steatosis of liver. Hum Pathol. 2011;42:356–360. - PMC - PubMed
    1. Schadt EE, Molony C, Chudin E, et al. Mapping the genetic architecture of gene expression in human liver. PLoS Biol. 2008;6(5):e107. - PMC - PubMed
    1. Smith BW, Adams LA. Nonalcoholic fatty liver disease and diabetes mellitus: pathogenesis and treatment. Nat Rev Endocrinol. 2011;7:456–465. - PubMed
    1. Cox AJ, Wing MR, Carr JJ, et al. Association of PNPLA3 SNP rs738409 with liver density in African Americans with type 2 diabetes mellitus. Diabetes Metab. 2011;37(5):452–455. - PMC - PubMed

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