Department of Clinical and Chemical Pathology, Faculty of Medicine, Cairo University, El Saray St., El Manial, 11956, Cairo, Egypt,
Mol Diagn Ther. 2014 Jun;18(3):343-54. doi: 10.1007/s40291-014-0084-5.
Chronic obstructive pulmonary disease (COPD) is a complex chronic inflammatory disease that involves the activity of various inflammatory cells and mediators. It has been suggested that susceptibility to COPD is, at least in part, genetically determined. The primary aim of this study was to investigate the association between surfactant protein D (SFTPD) rs2243639, interleukin (IL)-1β rs16944 and IL-1 receptor antagonist (IL-1RN) rs2234663 gene polymorphisms and COPD susceptibility, as well as examining the association between the various IL-1RN/IL-1β haplotypes and pulmonary function tests (PFT). Secondly, we aimed to examine the influence of SFTPD rs2243639 polymorphism on serum surfactant protein D (SP-D) level.
A total of 114 subjects were recruited in this study and divided into three groups: 63 COPD patients, 25 asymptomatic smokers, and 26 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed for the detection of SFTPD rs2243639 and IL-1β rs16944 polymorphisms. Detection of variable numbers of an 86-bp tandem repeat (VNTR) of IL-1RN was done using PCR. Serum SP-D level was measured using enzyme linked-immunosorbent assay. PFTs were measured by spirometry.
Carriers of the SFTPD AG and AA polymorphic genotypes constituted 71.4 % of COPD patients versus 48 % in asymptomatic smokers, with a statistically significant difference between the two groups (p = 0.049). Smokers who were carriers of the polymorphic SFTPD rs2243639 A allele (AG and AA genotypes) have a 2.708 times risk of developing COPD when compared with wild-type GG genotype carriers [odds ratio (OR) 2.708 (95 % CI 1.041-7.047)]. Forced expiratory flow (FEF) 25-75 % predicted was higher in IL-1RN*1/*1 when compared with *1/*2 (p = 0.013). FEF25-75 % predicted in carriers of haplotype IL-1RN *1/IL-1β T (49.21 ± 10.26) was statistically significantly higher than in carriers of IL-1RN *2/IL-1β T (39.67 ± 12.64) [p = 0.005]. Forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) in carriers of haplotype IL-1RN *1/IL-1β T (64.09 ± 6.39) was statistically significantly higher than in carriers of IL-1RN *2/IL-1βT (59.44 ± 7.71) [p = 0.048]. There was no association between SFTPD rs2243639 genotypes and serum SP-D level.
Smokers who are carriers of the SFTPD AG and AA polymorphic genotypes may be at a higher risk of developing COPD when compared with wild-type GG genotype carriers. IL-1RN rs2234663/IL-1β rs16944 haplotypes influence FEF25-75 % predicted and FEV1/FVC. SFTPD rs2243639 polymorphism did not influence serum SP-D levels in our group of recruited subjects.
慢性阻塞性肺疾病（COPD）是一种复杂的慢性炎症性疾病，涉及多种炎症细胞和介质的活性。有人认为，COPD 的易感性至少部分是由遗传决定的。本研究的主要目的是探讨表面活性剂蛋白 D（SFTPD）rs2243639、白细胞介素（IL）-1β rs16944 和 IL-1 受体拮抗剂（IL-1RN）rs2234663 基因多态性与 COPD 易感性的关系，并研究不同的 IL-1RN/IL-1β 单倍型与肺功能测试（PFT）之间的关系。其次，我们旨在研究 SFTPD rs2243639 多态性对血清表面活性剂蛋白 D（SP-D）水平的影响。
本研究共招募了 114 名受试者，分为三组：63 名 COPD 患者、25 名无症状吸烟者和 26 名健康对照者。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）检测 SFTPD rs2243639 和 IL-1β rs16944 多态性。采用聚合酶链反应检测白细胞介素 1 受体拮抗剂（IL-1RN）的 86bp 串联重复（VNTR）的可变数目。采用酶联免疫吸附试验测定血清 SP-D 水平。通过肺活量计测量 PFT。
COPD 患者中携带 SFTPD AG 和 AA 多态基因型的比例为 71.4%，而无症状吸烟者为 48%，两组间有统计学差异（p=0.049）。与野生型 GG 基因型携带者相比，携带多态性 SFTPD rs2243639 A 等位基因（AG 和 AA 基因型）的吸烟者患 COPD 的风险增加 2.708 倍[比值比（OR）2.708（95%置信区间 1.041-7.047）]。与 IL-1RN1/2 相比，IL-1RN1/1 时 25%至 75%预计用力呼气流量（FEF）更高（p=0.013）。携带 IL-1RN1/IL-1β T 单倍型的受试者的 FEF25-75%预计值（49.21±10.26）明显高于携带 IL-1RN2/IL-1β T 单倍型的受试者（39.67±12.64）[p=0.005]。携带 IL-1RN1/IL-1β T 单倍型的受试者的 1 秒用力呼气容积（FEV1）/用力肺活量（FVC）比值（64.09±6.39）明显高于携带 IL-1RN2/IL-1β T 单倍型的受试者（59.44±7.71）[p=0.048]。SFTPD rs2243639 基因型与血清 SP-D 水平之间无关联。
与野生型 GG 基因型携带者相比，携带 SFTPD AG 和 AA 多态基因型的吸烟者可能有更高的患 COPD 的风险。IL-1RN rs2234663/IL-1β rs16944 单倍型影响 FEF25-75%预计值和 FEV1/FVC。SFTPD rs2243639 多态性未影响我们组招募的受试者的血清 SP-D 水平。
