Dataset Information

Association of the MMP7 -181A>G Promoter Polymorphism with Early Onset of Chronic Obstructive Pulmonary Disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is characterized by decreased air flow and is associated with abnormal chronic inflammation in the airways and extensive tissue remodeling. Matrix metalloproteinase-7 (MMP7) is produced primarily by the epithelium of many organs, including the lungs. A functional MMP7 -181A>G (rs11568818) promoter polymorphism influences the binding of nuclear regulatory proteins modulating the transcription of the gene. In this study, we genotyped 191 patients with COPD for MMP7 -181A>G single nucleotide polymorphism (SNP) and 215 control subjects using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and explored the role of that polymorphism as a risk factor for COPD. There were no differences in the genotype and allele distribution of the MMP7 -181A>G SNP between the COPD patients and control groups (p = 0.341 and p = 0.214). However, the carries of the G allele (AG and GG genotypes), appeared to develop COPD significantly earlier than those with the AA genotype (61.01 ± 10.11 vs. 64.87 ± 9.00 years, p = 0.032). When the genotype distribution was studied only in the groups of patients (n = 76) and controls (n = 106) younger than 60 years, we found significantly higher frequency of the carriers of the G allele in COPD patients than in the controls, determining about a 3-fold higher risk for COPD [odds ratio (OR) -3.33, 1.36-8.14, p = 0.008 for GG, and OR = 2.91, 1.38-6.13, p = 0.005 for AG+GG]. Based on our results, the MMP7 -181A>G promoter variant may influence early development of COPD. This effect could be attributed to the increased production of the enzyme resulting in enhanced airway wall protein degradation and injury.

SUBMITTER: T T

PROVIDER: S-EPMC5972504 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Association of the MMP7 -181A>G Promoter Polymorphism with Early Onset of Chronic Obstructive Pulmonary Disease.

T Tacheva T D Dimov D A Anastasov A Y Zhelyazkova Z M Kurzawski K M Gulubova G M Drozdzik D T Vlaykova V

Balkan journal of medical genetics : BJMG 20171229 2

Chronic obstructive pulmonary disease (COPD) is characterized by decreased air flow and is associated with abnormal chronic inflammation in the airways and extensive tissue remodeling. Matrix metalloproteinase-7 (MMP7) is produced primarily by the epithelium of many organs, including the lungs. A functional MMP7 -181A>G (rs11568818) promoter polymorphism influences the binding of nuclear regulatory proteins modulating the transcription of the gene. In this study, we genotyped 191 patients with C ...[more]

PMID: 29876234

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Project description:Despite being a major cause of morbidity and mortality, chronic obstructive pulmonary disease (COPD) is frequently undiagnosed. Yet the burden of disease among the undiagnosed is significant, as these individuals experience symptoms, exacerbations, and excess mortality compared to those without COPD. The U.S. Preventive Services Task Force recommends against routine screening of asymptomatic individuals with spirometry. Hence, case-finding approaches are needed. A recently developed instrument, the five-item COPD Assessment in Primary Care to Identify Undiagnosed Respiratory Disease and Exacerbation Risk questionnaire plus peak expiratory flow, demonstrates good sensitivity and specificity for distinguishing cases from control subjects and is being studied prospectively in primary care settings to determine its impact on patient outcomes. However, finding the undiagnosed is only half the battle. Mounting evidence suggests significant COPD-like respiratory burden among individuals without airflow obstruction. Many experience dyspnea, mucus production, and exacerbation events and have emphysema and airway abnormalities on computed tomographic (CT) imaging of the chest. However, it is still unclear how to best treat these individuals and which individuals go on to develop spirometric obstruction. These challenges underline the importance of defining what constitutes "early disease." A recently proposed definition characterizes early COPD as either: 1) airflow limitation, 2) compatible CT imaging abnormalities, or 3) accelerated forced expiratory volume in 1 second decline in persons younger than 50 years and with greater than a 10 pack-year smoking history. Although it is recognized that this definition does not encompass all individuals who will develop COPD, it is an attempt to identify a group of individuals with most rapid decline to better understand mechanisms of disease development and where disease-modifying interventions are most likely to be successful. Ultimately, leveraging tools such as chest CT imaging, the electronic medical record, and machine learning algorithms may aid in the identification of such individuals.

Project description:BackgroundThe association between the oxidative stress gene polymorphism and chronic obstructive pulmonary disease (COPD) risk has been extensively studied but the results have been controversial. This study aimed to investigate the overall association between the oxidative stress gene including glutathione S-transferase (GST), epoxide hydrolase exon (EPHX), superoxide dismutase (SOD), catalase (CAT), cytochrome P450 system (CYP) and heme oxygenase (HO-1) polymorphism and the risk of COPD.MethodsWe searched the PubMed and EMBASE database to identify studies that investigated the association between the oxidative stress gene polymorphism and risk of COPD. The relevant data were extracted and statistical analyses were performed using the Revman 5.4 and STATA 12 software. Dominant genetic model, recessive model, co-dominant model, heterozygote model, and allele model were analyzed. Venice criteria and publication bias were conducted to access the credibility and reliability.ResultsIn total, 63 publications including 14,733 patients and 50,570 controls were included in the meta-analysis.15 genetic variants of 6 genes were analyzed, and 7 SNPs in GSTP1, CAT, CYP, SOD were first analyses until now. In our study, EPHX T113C C allele, GSTM1 null, GSTT1 null, GSTP1 A313G G and C341T T allele, CYP1A1 MspI C allele, SOD3 A213G G allele and L type in Ho-1 showed increased COPD risk, especially in Asians. T allele in CAT C262T and C allele in SOD2 Val 9 Ala were associated with decreased COPD risk. To avoid high heterogeneity and publications bias, subgroups analysis was performed in accord with HWE and ethnicity. Publication bias was assessed by Begg's funnel plots and Egger's test, and no publication bias were found for recessive models. 4 variants were identified with strong levels of epidemiological evidence of associations with the COPD risk.ConclusionsOur results confirm that oxidative stress gene polymorphism was associated with COPD risk. These finding can improve human understanding of this disease gene molecular level and enable early intervention and prevention of COPD. Well-designed studies with large sample sizes are essential to clarify the association of these significant variants with the susceptibility to COPD.

Dataset Information

Association of the MMP7 -181A>G Promoter Polymorphism with Early Onset of Chronic Obstructive Pulmonary Disease.

Publications

Association of the MMP7 -181A>G Promoter Polymorphism with Early Onset of Chronic Obstructive Pulmonary Disease.

Similar Datasets

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