Department of Biotechnology, University of Kashmir, Srinagar, J&K, 190006, India.
Institute of Biomedical Sciences, University of Chile, 8380453, Santiago, Chile.
Lung. 2018 Aug;196(4):447-454. doi: 10.1007/s00408-018-0124-8. Epub 2018 May 26.
Different mutations in coding and non-coding sequences of the SERPINA1 gene have been implicated in the pathogenesis of COPD. However, - 10T/C mutation in the hepatocyte-directed promoter region has not been associated with COPD pathogenesis so far. Here, we report an increased frequency of - 10C genotype that is associated with decreased levels of serum alpha1-antitrypsin (α1AT) in COPD patients.
The quantification of serum α1AT was done by ELISA, the phenol-chloroform method was used for DNA extraction, PCR products were directly sequenced. The IBM SPSS Statistics v21 software was used for statistical analyses of the data.
The mean serum α1AT level was found to be 1.203+0.239 and 3.162+0.160 g/L in COPD cases and in control, respectively. The - 10C allele is associated with an increased risk of COPD [OR, 3.50 (95%CI, 1.86-6.58); p < 0.001]. The combined variant genotype (TT+CC) was significantly found associated with an increased risk of COPD [OR, 3.20 (95% CI, 1.47-6.96); p = 0.003]. A significant association of the family history with COPD (overall p value= 0.0331) suggests that genetics may play an important role in the pathogenesis of COPD.
The polymorphism associated with hepatocyte-specific promoter region (- 10T/C) is likely to be associated with the pathogenesis of COPD. It is quite possible that the change of the base in the hepatocyte-specific promoter of the SERPINA1 gene can modulate its strength, thereby driving the reduced expression of α1AT.
SERPINA1 基因编码和非编码序列中的不同突变与 COPD 的发病机制有关。然而，到目前为止，肝细胞定向启动子区域的-10T/C 突变与 COPD 发病机制无关。在这里，我们报告了-10C 基因型的频率增加，与 COPD 患者血清α1-抗胰蛋白酶（α1AT）水平降低有关。
通过 ELISA 定量测定血清α1AT，酚-氯仿法提取 DNA，PCR 产物直接测序。使用 IBM SPSS Statistics v21 软件对数据进行统计分析。
发现 COPD 病例和对照组的血清α1AT 水平平均值分别为 1.203+0.239 和 3.162+0.160 g/L。-10C 等位基因与 COPD 的发病风险增加相关[OR，3.50（95%CI，1.86-6.58）；p<0.001]。联合变异基因型（TT+CC）与 COPD 的发病风险显著相关[OR，3.20（95%CI，1.47-6.96）；p=0.003]。家族史与 COPD 之间存在显著关联（总 p 值=0.0331），表明遗传可能在 COPD 的发病机制中起重要作用。
与肝细胞特异性启动子区域相关的多态性（-10T/C）可能与 COPD 的发病机制有关。SERPINA1 基因肝细胞特异性启动子中的碱基变化很可能调节其强度，从而导致α1AT 的表达降低。
