Aquino-Gálvez Arnoldo, González-Ávila Georgina, Pérez-Rodríguez Martha, Partida-Rodríguez Oswaldo, Nieves-Ramírez Miriam, Piña-Ramírez Inocencio, Ramírez-Martínez Gustavo, Castillejos-López Manuel, Checa Marco, Ruiz Victor, Urrea Francisco, Sommer Bettina, Zúñiga Joaquin, Selman Moisés
Instituto Nacional de Enfermedades Respiratorias "Ismael Cosío Villegas" Tlalpan 4502, Col. Sección XVI, 14080, Mexico, México.
Hospital General de México, Universidad Nacional Autónoma de México, Laboratorio de Inmunología, Mexico, Mexico.
BMC Pulm Med. 2015 Oct 24;15:129. doi: 10.1186/s12890-015-0127-7.
Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiology. Genetic variation within different major histocompatibility complex (MHC) loci contributes to the susceptibility to IPF. The effect of 70 kDa heat shock proteins (HSP70) gene polymorphisms in the susceptibility to IPF is unknown. The aim of this study was to explore the association between HSP70 polymorphisms and IPF susceptibility in the Mexican population.
Four HSP70 single nucleotide polymorphisms (SNPs) were evaluated using real time PCR assays in 168 IPF patients and 205 controls: +2763 C>T of HSPA1L (rs2075800), +2437 of HSP HSPA1L A>G (rs2227956), +190 of HSPA1A G>C (rs1043618) and +1267 of HSPA1B G>A (rs1061581).
The analysis of the recessive model revealed a significant decrease in the frequency of the genotype HSPA1B AA (rs1061581) in IPF patients (OR = 0.27, 95 % CI = 0.13-0.57, Pc = 0.0003) when compared to controls. Using a multivariate logistic regression analysis in a codominant model the HSPA1B (rs1061581) GA and AA genotypes were associated with a lower risk of IPF compared with GG (OR = 0.22, 95 % CI = 0.07-0.65; p = 0.006 and OR = 0.17, 95 % CI = 0.07-0.41; p = <0.001). Similarly, HSPA1L (rs2227956) AG genotype (OR = 0.34, 95 % CI = 0.12-0.99; p = 0.04) and the dominant model AG + GG genotypes were also associated with a lower risk of IPF (OR = 0.24, 95 % CI = 0.08-0.67; p = 0.007). In contrast, the HSPA1L (rs2075800) TT genotype was associated with susceptibility to IPF (OR = 2.52, 95 % CI = 1.32-4.81; p = 0.005).
Our findings indicate that HSPA1B (rs1061581), HSPA1L (rs2227956) and HSPA1 (rs1043618) polymorphisms are associated with a decreased risk of IPF.
特发性肺纤维化(IPF)是一种病因不明的致命性肺部疾病。不同主要组织相容性复合体(MHC)位点内的基因变异会导致IPF易感性增加。70 kDa热休克蛋白(HSP70)基因多态性对IPF易感性的影响尚不清楚。本研究旨在探讨墨西哥人群中HSP70多态性与IPF易感性之间的关联。
采用实时PCR分析对168例IPF患者和205例对照进行了4种HSP70单核苷酸多态性(SNP)评估:HSPA1L的+2763 C>T(rs2075800)、HSP HSPA1L的+2437 A>G(rs2227956)、HSPA1A的+190 G>C(rs1043618)和HSPA1B的+1267 G>A(rs1061581)。
隐性模型分析显示,与对照组相比,IPF患者中HSPA1B AA基因型(rs1061581)的频率显著降低(OR = 0.27,95%CI = 0.13 - 0.57,Pc = 0.0003)。在共显性模型中进行多因素逻辑回归分析时,与GG基因型相比,HSPA1B(rs1061581)的GA和AA基因型与IPF风险降低相关(OR = 0.22,95%CI = 0.07 - 0.65;p = 0.006和OR = 0.17,95%CI = 0.07 - 0.41;p = <0.001)。同样,HSPA1L(rs2227956)的AG基因型(OR = 0.34,95%CI = 0.12 - 0.99;p = 0.04)以及显性模型AG + GG基因型也与IPF风险降低相关(OR = 0.24,95%CI = 0.08 - 0.67;p = 0.007)。相反,HSPA1L(rs2075800)的TT基因型与IPF易感性相关(OR = 2.52,95%CI = 1.32 - 4.81;p = 0.005)。
我们的研究结果表明,HSPA1B(rs1061581)、HSPA1L(rs2227956)和HSPA1(rs1043618)多态性与IPF风险降低相关。