Lack of association between SREBF-1c gene polymorphisms and risk of non-alcoholic fatty liver disease in a Chinese Han population

Abstract

The transcription factor sterol regulatory element-binding protein-1c (SREBP-1c) is a key regulator of lipogenesis and insulin sensitivity, and is associated with non-alcoholic fatty liver disease (NAFLD). Here, we assessed the impact of common single nucleotide polymorphisms (SNPs) in SREBF-1c on NAFLD susceptibility and associated metabolic phenotypes in a Han Chinese population. Four common SNPs (rs62064119, rs2297508, rs11868035 and rs13306741) in the SREBP-1c gene were selected and genotyped in 593 patients with NAFLD and 593 healthy controls. Unconditional logistic regression was performed to assess the risk of NAFLD by determining odds ratios and 95% confidence intervals (CIs). No significant differences in genotype and allele frequencies of these four SNPs were found between the NAFLD population and the controls (all P > 0.05). In addition, we did not find any association between the SREBF-1c SNPs and the clinical and biochemical parameters, such as body mass index, total cholesterol, high density lipoprotein-and low density lipoprotein-cholesterol or systolic and diastolic blood pressure, except that the rs2297508 C-allele or rs11868035 G-allele showed significant associations with lower triglyceride levels in control subjects (P < 0.01). Our findings suggested that the four polymorphisms in SREBF-1c gene are not associated with risk of NAFLD in the Chinese Han population.

SREBF1c and SREBF2 gene polymorphisms are associated with acute coronary syndrome and blood lipid levels in Mexican population

“…In addition, we found that the G allele of the SREBF-1c 3’UTR A30225G (rs11868035) was associated with lower triglyceride levels. In the same way, Peng et al reported that the G allele of the SREBF-1c 3’UTR A30225G (rs11868035) was associated with lower triglyceride levels in non-alcoholic fatty liver disease [19]. Additionally, using bioinformatics tools we determined the potential effect of the SREBF2 and SREBF-1c gene polymorphisms associated with ACS.…”

“…Similarly, in a Danish population, Grarup et al reported in a meta-analysis study that the G allele is associated with a higher risk of T2DM [30]. However, Peng et al studied a Chinese Han population and reported that the 3’UTR A 30225 G and 3’UTR G30009C polymorphisms were not associated with risk of non-alcoholic fatty liver disease (NAFLD) [19]. With regard to the 3’UTR A30225G (rs11868035) polymorphism, we found that the G allele was associated with lower risk of developing ACS.…”

“…Moreover, in our study, the association of the SREBF2 G1784C (rs2228314) and SREBF-1c 3’UTR A30225G (rs11868035) polymorphisms with the presence ACS were positive, but controversial with other populations. We think that the association of the SREBF1c and SREBF2 polymorphisms could be due to the classical cardiovascular risk factors, and the environmental factors such as diet, exercise and lifestyle that have an important role in the development of the inflammatory diseases [19,33], as well as, to the fact that the allelic distribution of these polymorphisms varies according to the ethnic origin of the study populations. In this context, data obtained from the National Center for Biotechnology Information, showed that Caucasian population presents a higher frequency of the G allele of the 3’UTR A30225G (rs11868035) SNP (72%) when compared to Mexican Mestizos and Asian population that present a lower frequency of the G allele (41% and 16%, respectively).…”

“…Recently three single nucleotide polymorphism (SNPs) of the SREBF-1c isoform: two in the 3’UTR region [positions A30225G (rs11868035) and G30009C (rs2297508)], and one in intron 1 [position IVS1 G954A (rs11656665)] have been associated with T2DM, hypercholesterolemia, and adiponectin levels [8,9,18]. Nonetheless, the association of these polymorphisms with other inflammatory diseases such as ischemic stroke and non-alcoholic fatty liver disease is controversial with negative results [11,19]. On the other hand, the SREBF-2 gene presents two relevant SNPs in the intronic region [at positions IVSI C8407T (rs2267439) and IVSI2 A1667G (rs2267443), respectively] and one in the exon 10 [at position G1784C Gly595Ala (rs2228314 has merged into rs4822063)].…”

Improving Cognition to Increase Treatment Efficacy in Schizophrenia: Effects of Metabolic Syndrome on Cognitive Remediation's Outcome

“…For the analysis, patients were grouped in G/G homozygous vs. carriers of the A allele, as in previous literature (33).…”