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Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans.

ABSTRACT: The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promoter activity and thereby the gene expression. Genotyping through polymerase chain reaction (PCR) and subsequent automatic sequencing was done in 167 patients with bronchiectasis and their age-, sex-matched healthy controls to reveal that only -799C/T is polymorphic among Koreans. In the patient group with bronchiectasis, the frequency of -799C/C, C/T, and T/T genotypes were 41.9%, 49.7%, and 8.4%, respectively. A similar distribution was observed in the control group: C/C (49.7%), C/T (43.1%), and T/T (7.2%) (p=0.36). In subgroup analysis, no significant difference was observed among the patients according to; the extent of disease (p=0.76), colonization of microorganisms (p=0.56), or association of mycobacteria (p=0.17). From these results, we conclude that -799C/T on the promoter region of MMP-8 lacks association with development of bronchiectasis in Koreans.

SUBMITTER: Lee J

PROVIDER: S-EPMC2693817 | biostudies-literature | 2007 Aug

REPOSITORIES: biostudies-literature

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Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans.

Lee Jiwon J Kim Hye Ryoun HR Min Joo Won JW Park Jong Sun JS Jin Sang Man SM Han Sung Koo SK Shim Young Soo YS Yim Jae Joon JJ

Journal of Korean medical science 20070801 4

The observation that human matrix metalloproteinase (MMP)-8 is over-expressed in ectatic bronchi in patients with bronchiectasis suggests that polymorphisms altering the expression of MMP-8 may contribute to the susceptibility to development of bronchiectasis. We evaluated the association between the presence of bronchiectasis in a Korean population and two single nucleotide polymorphisms (SNPs) (-799C/ T and -381A/G) on the promoter region of the MMP-8 gene that are reported to alter the promot ...[more]

PMID: 17728507

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Project description:BackgroundThe role of matrix metalloproteinase (MMP) gene polymorphisms in the development of chronic obstructive pulmonary disease (COPD) has been reported with inconsistent results. This meta-analysis was performed to assess the association of MMP-1 -1607G/GG and MMP-9 -1562C/T promoter polymorphisms with COPD susceptibility.MethodsPublished case-control studies from Pubmed and China National Knowledge Infrastructure (CNKI) databases were retrieved. Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated.ResultsA total of fourteen case-control studies were included in this meta-analysis. Pooled effect size showed an association of MMP-9 -1562 C/T with the risk of COPD (dominant model: TT+CT vs CC; OR: 1.46; 95% CI: 1.02-2.08; p = 0.04). However, no correlation with COPD was revealed in MMP-1 -1607G/GG polymorphism. When stratified by ethnicity, results indicated MMP-1 -1607G/GG (recessive model: G/G vs G/GG+GG/GG; OR: 1.20; 95% CI: 1.01-1.44; p = 0.04) and MMP-9 -1562 C/T (dominant model; OR: 1.66; 95% CI: 1.01-2.71; p = 0.04) were correlated with COPD susceptibility among Caucasians and Asians respectively. According to source of controls, significant association of MMP-9 -1562 C/T (additive model: T vs C; OR:1.71, 95% CI: 1.42-2.07; p<0.00001, and dominant model; OR: 1.92; 95% CI: 1.34-2.76; p = 0.0004) with COPD susceptibility was revealed in the subgroup with smoker-based controls. However, in the aforementioned risk estimates, only the association of MMP-9 -1562 C/T (additive and dominant models) with the risk of COPD in the subgroup with smoker-based controls persisted significantly after Bonferroni correction for multiple testing. Moreover, after excluding the studies without Hardy-Weinberg equilibrium and/or with small sample size, the pooled results were robust and no publication bias was found in this study.ConclusionThis meta-analysis suggests, when using healthy smokers as controls, MMP-9 -1562 C/T, but not MMP-1 -1607 G/GG polymorphism is associated with the risk of COPD.

Project description:ContextThe exact factors that determine the biological behavior of odontogenic lesions have not been thoroughly established yet. The influence of the matrix metalloproteinases (MMPs) on the clinical behavior of these lesions was recently brought to light.AimsWe did a pioneer study to investigate the association of MMP9 (rs3918242 [-1562 C/T] and rs17576) and MMP2 (rs243865 [-1306 C/T] and rs865094) gene polymorphisms and aggressiveness of ameloblastomas, keratocystic odontogenic tumors (KCOT) and dentigerous cysts (DC).Settings and designA case-control study conducted in the Department of Oral Pathology and Microbiology, Government Dental College, Trivandrum and Human Molecular Genetics Laboratory, Rajiv Gandhi Institute of Biotechnology and Poojappura, Trivandrum, Kerala.Subjects and methodsDNA from the blood samples of histopathologically proven ameloblastoma (n = 15), KCOT (n = 11) and DC (n = 13) patients were extracted using standard protocols. Primers were designed based on the functionality and relevance for polymerase chain reaction (PCR). PCR products were analyzed by PCR-restriction fragment length polymorphism and sequencing.Statistical analysis usedChi-square analysis was done to assess the association of gene polymorphisms among the cases and controls.ResultsAmeloblastomas showed a higher frequency of mutant allele (T = 0.43; P = 0.05) of MMP9 rs3918242 (-1562C/T) compared to the control population. All the cases showed a statistically significant difference in the distribution of genotype (P = 0.046) and allele (P = 0.03; odds ratio [OR] = 2.06 [1.08-3.95]) frequency of MMP2 rs2438659 (-1306C/T). KCOT samples also showed a significant association in distribution of both genotype (P = 0.01) and allele (P = 0.01 with an OR at 3.42 [1.31-8.92]) frequency, on comparison with control population.ConclusionsMMP2 rs243865 polymorphism has a plausible role in increasing the aggressiveness of ameloblastomas and KCOT compared to that of the control population. Furthermore, MMP9 rs3918242 polymorphism may contribute to the aggressive behavior of ameloblastomas.

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Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans.

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Lack of association between matrix metalloproteinase 8 promoter polymorphism and bronchiectasis in Koreans.

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