title: 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 χ(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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.|Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Guanting
authors.initials: G
authors.lastname: Lu
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Ziyan
authors.initials: Z
authors.lastname: Wu
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Si
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Xiaoting
authors.initials: X
authors.lastname: Wen
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Haoze
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Blood Transfusion, Tangdu Hospital, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shijie
authors.initials: S
authors.lastname: Mu
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Fengchun
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Rheumatology and Clinical Immunology, Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Ministry of Education, Beijing, China.
authors.forename: Yongzhe
authors.initials: Y
authors.lastname: Li
keywords: HELZ2; Lipid metabollism; Primary biliary cirrhosis; Replication study