The dual and opposite role of the TM6SF2‐rs58542926 variant in protecting against cardiovascular disease and conferring risk for nonalcoholic fatty liver: A meta‐analysis

The aim of this work was to estimate the strength of the effect of the TM6SF2 E167K (rs58542926 C/T) variant on blood lipid traits and nonalcoholic fatty liver disease (NAFLD) across different populations. We performed a systematic review by a meta‐analysis; literature searches identified 10 studies...

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Published in:Hepatology (Baltimore, Md.) Vol. 62; no. 6; pp. 1742 - 1756
Main Authors: Pirola, Carlos J., Sookoian, Silvia
Format: Journal Article
Language:English
Published: United States Wolters Kluwer Health, Inc 01.12.2015
Subjects:
Cardiovascular Diseases - blood
Cardiovascular Diseases - genetics
Cholesterol - blood
Hepatology
Humans
Membrane Proteins - genetics
Membrane Proteins - physiology
Non-alcoholic Fatty Liver Disease - blood
Non-alcoholic Fatty Liver Disease - epidemiology
Non-alcoholic Fatty Liver Disease - genetics
Risk
Triglycerides - blood
ISSN:0270-9139, 1527-3350, 1527-3350
Online Access:Get full text
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Summary:The aim of this work was to estimate the strength of the effect of the TM6SF2 E167K (rs58542926 C/T) variant on blood lipid traits and nonalcoholic fatty liver disease (NAFLD) across different populations. We performed a systematic review by a meta‐analysis; literature searches identified 10 studies. The rs58542926 exerts a significant role in modulating lipid traits, including total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C), triglycerides (TG), and NAFLD. However, this influence on lipids and NAFLD is opposite between genotypes in the dominant model of inheritance. Pooled estimates of random effects in 101,326 individuals showed that carriers of the minor T allele (EK+KK individuals), compared with subjects homozygous for the ancestral C allele (EE genotype), are protected from cardiovascular disease (CVD), showing lower levels of TC, LDL‐C, and TG; the differences in mean ± standard error (mg/dL) are −8.38 ± 1.56, −3.7 ± 0.9, and −9.4 ± 2.1, respectively. The rs58542926 variant was not associated with high‐density lipoprotein cholesterol in a large sample (n = 91,937). In contrast, carriers of the T allele showed a moderate effect on the risk of NAFLD (odds ratio: 2.13; 95% confidence interval: 1.36–3.30; P = 0.0009; n = 3273) and approximately ∼2.2% higher lipid fat content when compared with homozygous EE (n = 3,413). Conclusions: The rs58542926 appears to be an important modifier of blood lipid traits in different populations. As a challenge for personalized medicine, the C‐allele, which has an overall frequency as high as 93%, is associated with higher blood lipids, whereas the T allele confers risk for NAFLD; in turn, CVD and NAFLD are strongly related outcomes. Although the variant confers protection against CVD at the expense of an increased risk of NAFLD, it does not explain the link between these two complex diseases.(Hepatology 2015;62:1742–1756)
Bibliography:Potential conflict of interest: Nothing to report.
This study was partially supported by grants PICT 2010‐0441 and PICT 2012‐0159 (Agencia Nacional de Promocioen CientÚfica y Tecnológica).
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ISSN:0270-9139
1527-3350
1527-3350
DOI:10.1002/hep.28142