Associations of MMP1, MMP2 and MMP3 Genes Polymorphism with Coal Workers’ Pneumoconiosis in Chinese Han Population

Coal workers’ pneumoconiosis (CWP) has been associated with abnormalities in the extracellular matrix remodeling, as well as aberrant matrix metalloproteinases (MMPs) in lung tissues. We investigated the association of three functional polymorphisms in MMP gene promoters (MMP1 rs1799750, MMP2 rs2285053 and MMP3 rs522616) with the risk of CWP. A total of 693 CWP cases and 690 controls were included in a case-control study. Genotype analysis was performed by the TaqMan method. Statistically significant differences were found in distributions of MMP3 rs522616 under a recessive model (p = 0.047) between CWP cases and controls. In the stratification analysis, individuals with MMP3 rs522616 GG genotype decreased the risk of CWP (adjusted OR = 0.72, 95% CI = 0.52–0.99) compared to those with AA/AG genotype obviously, particularly among subgroups of no smokers (adjusted OR = 0.64, 95% CI = 0.41–1.00). Furthermore, serum MMP3 protein levels measured with enzyme-linked immune-sorbent assay in the control group was significantly lower than that in the CWP groups (p = 0.02). Extremely lower MMP3 among subjects with the rs522616 GG or AG genotype compared with the AA genotype carriers (p < 0.05, p < 0.01 respectively) in the normal serum. These findings indicate that the MMP3 rs522616 polymorphism may contribute to the etiology of CWP in the Chinese population and MMP3 might be a potential diagnostic biomarker for CWP, additional independent studies are warranted to validate our findings in different populations as well as in a larger series

Associations of MMP-7 and OPN gene polymorphisms with risk of coal workers’ pneumoconiosis in a Chinese population: a case-control study

<p><i>Background</i>: The matrix metalloproteinase-7 (MMP-7) and osteopontin (OPN) are both multifunctional proteins with roles in inflammation, cell proliferation, tissue remodeling and so on, implicated in the pathogenesis of numerous conditions including pulmonary fibrosis. In this study, we investigated the associations between the potential functional polymorphisms in <i>MMP-7</i> and <i>OPN</i> and the risk of coal workers’ pneumoconiosis (CWP) in a Chinese population.</p> <p><i>Methods</i>: Four polymorphisms (rs10502001 in <i>MMP-7</i>, rs1126772, rs11728697 and rs9138 in <i>OPN</i>) were genotyped and analyzed in a case-control study of 697 CWP and 694 control subjects.</p> <p><i>Results</i>: Our results revealed that three single nucleotide polymorphisms (SNPs, <i>MMP-7</i> rs10502001, <i>OPN</i> rs1126772 and <i>OPN</i> rs11728697) were associated with increased risk of CWP under a recessive model (adjusted odds ratio [OR] = 1.80, 95% confidence interval [CI] = 1.01–3.20, <i>p</i> = 0.045 for <i>MMP-7</i> rs10502001; adjusted OR = 2.09, 95% CI = 1.17–3.72, <i>p</i> = 0.013 for <i>OPN</i> rs1126772; adjusted OR = 2.48, 95% CI = 1.37–4.51, <i>p</i> = 0.003 for <i>OPN</i> rs11728697). Additionally, a combined effect was observed in a dose-dependent manner with increasing numbers of risk variant alleles (<i>P</i>_trend = 0.003). Furthermore, logistic regression analysis revealed no significant interaction between SNPs and smoking status on CWP risk.</p> <p><i>Conclusions</i>: Our results indicate that three functional SNPs (<i>MMP-7</i> rs10502001, <i>OPN</i> rs11728697 and <i>OPN</i> rs1126772) are associated with an increased risk of CWP in a Chinese population.</p

Polymorphisms in <i>SPARC</i> and Coal Workers' Pneumoconiosis Risk in a Chinese Population

<div><p>Background</p><p>The 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 <i>SPARC</i> and coal workers' pneumoconiosis (CWP) risk in a Chinese population.</p><p>Methods</p><p>Five potentially functional polymorphisms (rs1059279, rs1059829, rs1053411, rs2304052 and rs4958281) in <i>SPARC</i> 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.</p><p>Results</p><p>Our 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, <i>P</i> = 0.015 for rs1059279; OR = 1.20, 95%CI = 1.03–1.39, <i>P</i> = 0.021 for rs1059829; OR = 1.31, 95%CI = 1.03–1.65, <i>P</i> = 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, <i>P</i> = 0.023). In the combined analysis of these five polymorphisms, individuals with multiple risk alleles had a higher risk of CWP (<i>P</i>trend = 0.015).</p><p>Conclusion</p><p>Our results indicate that three functional <i>SPARC</i> 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.</p></div

Stratification analyses between the genotypes of three SNPs and CWP risk.

a<p>Variant homozygote/Heterozygote/Wild type homozygote;</p>b<p>Adjusted for age, exposure years, pack-years smoked, and occupation.</p

Demographic and selected variables among the CWP cases and control subjects.

<p>Demographic and selected variables among the CWP cases and control subjects.</p

Function prediction of SNPs.

<p>Function prediction of SNPs.</p

Primary information of genotyped SNPs.

<p>dbSNP^a based on Asian in dbSNP;</p><p>HWE^b (Hardy–Weinberg equilibrium) <i>P</i> value of the control group.</p

Distributions of genotypes and their associations with risk of CWP.

a<p>Two-sided x² test.</p>b<p>Adjusted for age, exposure years, pack-years smoked, and occupation.</p