Polymorphisms in SPARC and Coal Workers' Pneumoconiosis Risk in a Chinese Population

BackgroundThe SPARC is a crucial matricellular protein and may influence the course of various diseases like tumor metastasis and fibrosis. In the present study, we investigated the association between the potential functional polymorphisms in SPARC and coal workers' pneumoconiosis (CWP) risk in a Chinese population.MethodsFive potentially functional polymorphisms (rs1059279, rs1059829, rs1053411, rs2304052 and rs4958281) in SPARC were genotyped and analyzed in a case-control study including 697 CWP cases and 694 controls. The genotyping was used by the TaqMan method with the ABI 7900HT Real Time PCR system.ResultsOur results revealed that three SNPs (rs1059279, rs1059829, rs1053411) were significantly associated with increased risk of CWP under an additive model (OR = 1.35, 95%CI = 1.06–1.71, P = 0.015 for rs1059279; OR = 1.20, 95%CI = 1.03–1.39, P = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03–1.65, P = 0.025 for rs1053411). In the stratification analysis, significant associations were observed between each of these three SNPs and patients with 0–20 pack-years of smoking (OR = 1.73, 95%CI = 1.21–2.45 for rs1059279; OR = 1.48, 95%CI = 1.07–2.05 for rs105982; OR = 1.58, 95%CI = 1.13–2.22 for rs1053411). Furthermore, the association between rs1059279 and CWP risk remained significant among subjects with over 27 years of exposure (OR = 1.27, 95%CI = 1.03–1.56, P = 0.023). In the combined analysis of these five polymorphisms, individuals with multiple risk alleles had a higher risk of CWP (Ptrend = 0.015).ConclusionOur results indicate that three functional SPARC SNPs are associated with an increased risk of CWP in a Chinese population. Further functional research and validation studies with diverse populations are warranted to confirm our findings.【背景】SPARC（分泌型酸性富含半胱氨酸蛋白）是一类关键的基质细胞蛋白，可影响肿瘤转移、纤维化等多种疾病的进程。本研究旨在探讨中国人群中SPARC潜在功能性多态性与煤工尘肺（coal workers' pneumoconiosis, CWP）发病风险的关联。 【方法】本研究采用病例-对照研究设计，纳入697例煤工尘肺患者与694例健康对照，对SPARC基因的5个潜在功能性单核苷酸多态性位点（rs1059279、rs1059829、rs1053411、rs2304052及rs4958281）进行基因分型与分析。基因分型采用TaqMan探针法，依托ABI 7900HT实时荧光定量PCR系统完成。 【结果】本研究结果显示，在加性遗传模型下，3个单核苷酸多态性位点（rs1059279、rs1059829、rs1053411）与煤工尘肺发病风险升高显著相关：rs1059279的比值比（OR）为1.35，95%置信区间（95%CI）为1.06~1.71，P=0.015；rs1059829的OR为1.20，95%CI为1.03~1.39，P=0.021；rs1053411的OR为1.31，95%CI为1.03~1.65，P=0.025。分层分析结果表明，这3个位点均与吸烟包年数为0~20包的人群煤工尘肺发病风险显著相关：rs1059279的OR为1.73，95%CI为1.21~2.45；rs105982的OR为1.48，95%CI为1.07~2.05；rs1053411的OR为1.58，95%CI为1.13~2.22。此外，在接尘时长超过27年的人群中，rs1059279与煤工尘肺发病风险的关联仍具有统计学意义（OR=1.27，95%CI=1.03~1.56，P=0.023）。对5个多态性位点的联合分析显示，携带更多风险等位基因的个体罹患煤工尘肺的风险更高（趋势检验P=0.015）。 【结论】本研究结果表明，中国人群中3个功能性SPARC单核苷酸多态性位点与煤工尘肺发病风险升高显著相关。后续需开展更多功能性研究及不同人群的验证研究，以验证本研究结果。