A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.
A rare nonsynonymous variant in the lipid metabolic gene HELZ2 related to primary biliary cirrhosis in Chinese Han.
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脂质代谢基因HELZ2罕见非同义变异与中国汉族原发性胆汁性肝硬化相关
DOI：
10.1186/s13223-016-0120-6
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发表时间：
2016
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Li P;Lu G;Wang L;Cui Y;Wu Z;Chen S;Li J;Wen X;Zhang H;Mu S;Zhang F;Li Y
在欧洲和日本起源的原发性胆汁性肝硬化（PBC）的几个全基因组关联研究表明，PBC的易感性的几十个遗传位点的显着关联。大部分位点与免疫应答途径有关。本研究旨在探讨脂质代谢基因HELZ 2是否与PBC的发病机制有关。应用MassArray iPLEX对586例PBC患者（病例1组358例，病例2组201例）和726名健康对照者进行6个非同义SNPs基因分型。两组PBC病例均采用相同的对照组。等位基因频率采用2 × 2列联表进行χ2检验。使用PLINK工具集分析所有数据。计算比值比（OR）和95%置信区间（95% CI），认为p值（通过Bonferroni校正进行多重检验校正）小于0.05具有统计学显著性。rs79267778的A等位基因与PBC显著相关（OR组合= 4.204 [1.670-10.582]，pcombined = 1.87E−04）。其将位置1904（NM_001037335）处的氨基酸从苏氨酸（ACG）变更为蛋氨酸（ATG）。该位点在哺乳动物中高度保守，预测可能有损伤，PolyPhen-2评分为0.469。进一步预测T1904 M在pH7.0和37 °C条件下可提高蛋白质的稳定性，置信度为25.18%。本研究首次发现脂质代谢基因HELZ 2与自身免疫性疾病相关，至少在中国汉族PBC中是如此。
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. 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 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. The 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. 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.