Abstract
BackgroundSeveral genome-wide association studies of primary biliary cirrhosis (PBC) in European and Japanese origins have shown significant association of dozens of genetic loci contributive to the susceptibility of PBC. Most of the loci were related to immune response pathway. In this study, we tested whether the lipid metabolic gene HELZ2 was associated with the pathogenesis of PBC.MethodsIn 586 PBC cases (358 in case 1 group and 201 in case 2 group) and 726 healthy controls of Chinese Han, six nonsynonymous SNPs were genotyped by MassArray iPLEX. The same control were used for the two groups of PBC cases. Allele frequencies were calculated by χ2 test based on 2 × 2 contingency tables. All data were analyzed using the PLINK tool set. The odds ratio (OR) and 95 % confidence interval (95 % CI) were calculated, and p values (corrected for multiple testing by Bonferroni adjustment) less than 0.05 were considered statistically significant.ResultsThe A allele of rs79267778 was significantly associated with PBC (ORcombined = 4.204 [1.670–10.582], pcombined = 1.87E−04). It changed the amino acid at position 1904 (NM_001037335) from Threonine (ACG) to Methionine (ATG). This site was highly conserved in mammals and predicted to be POSSIBLY DAMAGING with a score of 0.469 by PolyPhen-2. It’s further predicted that T1904 M could INCREASE the protein stability with a confidence at 25.18 % under the condition of pH 7.0 and 37 °C.ConclusionThe result was the first time to show evidence of the lipid metabolic gene HELZ2 related to autoimmune disease, at least in PBC of Chinese Han.
Highlights
Several genome-wide association studies of primary biliary cirrhosis (PBC) in European and Japanese origins have shown significant association of dozens of genetic loci contributive to the susceptibility of PBC
The result was the first time to show evidence of the lipid metabolic gene HELZ2 related to autoimmune disease, at least in PBC of Chinese Han
HELZ2 was encircled by common deletion polymorphisms
Summary
Several genome-wide association studies of primary biliary cirrhosis (PBC) in European and Japanese origins have shown significant association of dozens of genetic loci contributive to the susceptibility of PBC. We tested whether the lipid metabolic gene HELZ2 was associated with the pathogenesis of PBC. HELZ2 [OMIM 611265], known as PRIC285 or PDIP1, is a 2649 amino acid nuclear helicase protein, being a part of the peroxisome proliferator activated receptor α interacting (PRIC) complex [2]. It functions as a nuclear transcriptional coactivator for PPARA and PPARG, as well as other nuclear receptors (RXRA, THRA, THRB) [2, 3]. Inferred from items of gene ontology, this gene is mainly related with cellular lipid metabolic process [4] and liver regeneration [5]
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