Dataset Information

A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.

ABSTRACT: BACKGROUND: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. 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. METHODS:In 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 ?(2) 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. RESULTS:The A allele of rs79267778 was significantly associated with PBC (ORcombined = 4.204 [1.670-10.582], p combined = 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. CONCLUSION: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.

SUBMITTER: Li P

PROVIDER: S-EPMC4819269 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.

Li Ping P Lu Guanting G Wang Li L Cui Ying Y Wu Ziyan Z Chen Si S Li Jing J Wen Xiaoting X Zhang Haoze H Mu Shijie S Zhang Fengchun F Li Yongzhe Y

Allergy, asthma, and clinical immunology : official journal of the Canadian Society of Allergy and Clinical Immunology 20160404

<h4>Background</h4>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. 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.<h4>Methods</h4>In 586 PBC cases (358 in case 1 group and 201 in case 2 group) and 726 healthy controls ...[more]

PMID: 27047549

Similar Datasets

Project description:Primary biliary cirrhosis (PBC) is an immune-mediated chronic cholestatic liver disease with a slowly progressive course. Without treatment, most patients eventually develop fibrosis and cirrhosis of the liver and may need liver transplantation in the late stage of disease. PBC primarily affects women (female preponderance 9-10:1) with a prevalence of up to 1 in 1,000 women over 40 years of age. Common symptoms of the disease are fatigue and pruritus, but most patients are asymptomatic at first presentation. The diagnosis is based on sustained elevation of serum markers of cholestasis, i.e., alkaline phosphatase and gamma-glutamyl transferase, and the presence of serum antimitochondrial antibodies directed against the E2 subunit of the pyruvate dehydrogenase complex. Histologically, PBC is characterized by florid bile duct lesions with damage to biliary epithelial cells, an often dense portal inflammatory infiltrate and progressive loss of small intrahepatic bile ducts. Although the insight into pathogenetic aspects of PBC has grown enormously during the recent decade and numerous genetic, environmental, and infectious factors have been disclosed which may contribute to the development of PBC, the precise pathogenesis remains enigmatic. Ursodeoxycholic acid (UDCA) is currently the only FDA-approved medical treatment for PBC. When administered at adequate doses of 13-15 mg/kg/day, up to two out of three patients with PBC may have a normal life expectancy without additional therapeutic measures. The mode of action of UDCA is still under discussion, but stimulation of impaired hepatocellular and cholangiocellular secretion, detoxification of bile, and antiapoptotic effects may represent key mechanisms. One out of three patients does not adequately respond to UDCA therapy and may need additional medical therapy and/or liver transplantation. This review summarizes current knowledge on the clinical, diagnostic, pathogenetic, and therapeutic aspects of PBC.

Dataset Information

A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.

Publications

A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets