Association of (-1,607) 1G/2G polymorphism of matrix metalloproteinase-1 gene with knee osteoarthritis in the Turkish population (knee osteoarthritis and MMPs gene polymorphisms)

The aim of this study was to investigate whether functional polymorphisms in the promoter of matrix metalloproteinase-1 (MMP-1), MMP-2 and MMP-9 genes were associated with susceptibility to knee osteoarthritis in the Turkish population. The MMP-1 −1,607 1G/2G (rs1799750), MMP-2 −1,306 C/T (rs243865), and MMP-9 −1,562 C/T (rs3918242) polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism assay in 157 patients diagnosed with knee osteoarthritis based on the criteria of American College of Rheumatology and in 84 controls in Mersin, Turkey. Genotype distributions and allele frequencies of MMP-1, MMP-2, and MMP-9 gene polymorphisms were compared between the patients and controls. There were significant differences between the groups regarding the genotype distribution of MMP-1 polymorphism (P  = 0.001). The frequencies of 1G/1G and 1G/2G genotypes were significantly higher in the knee osteoarthritis than in the controls (P = 0.002, and P =  0.006, respectively). In addition, 1G allele frequency of MMP-1 gene was higher in the patients than in the control group (P = 0.0001). The genotype distributions and allele frequencies of MMP-2 and MMP-9 gene polymorphisms did not differ between the osteoarthritis and the control groups (P > 0.05). These findings suggest that the −1,607 1G/2G polymorphism in the MMP-1 gene may contribute to susceptibility to knee osteoarthritis in the Turkish population.     

Association of a nonsynonymous single-nucleotide polymorphism of matrix metalloproteinase 9 with giant cell arteritis

OBJECTIVE: Giant cell arteritis (GCA) is the most common type of primary vasculitis. Matrix metalloproteinase 9 (MMP-9) is present in arterial lesions of GCA and may be involved in its pathogenesis. We investigated whether certain genotypes of 4 single-nucleotide polymorphisms (SNPs) of MMP-9 are overrepresented in patients with histologically confirmed GCA. METHODS: Four SNPs of MMP-9, rs3918242 in the promoter region and 3 nonsynonymous coding SNPs (rs3918252, rs17576, and rs2250889) were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 58 white patients for whom there was a clinical suspicion of GCA. Thirty of these patients had histologically confirmed GCA (group 1), and 28 patients had negative results of a temporal artery biopsy for GCA (group 2). Estimates of the genotype distributions of each of these SNPs in a white population were determined using publicly available genotype data for a panel of 23 individuals (group 3). RESULTS: Although 1 SNP was monomorphic in all 3 groups, we observed statistically significant differences in the genotype distributions for rs2250889 between group 1 and group 2 (P = 0.005) and between group 1 and group 3 (P = 0.009), but not between groups 2 and 3 (P = 0.965). CONCLUSION: These data derived from a sample of patients with GCA suggest that the G allele of MMP-9 polymorphism rs2250889 is overrepresented in patients with histologically confirmed GCA. Clearly, larger sample sizes will be necessary to confirm this suggestive association and better characterize a possible linkage disequilibrium structure among polymorphisms.     

Matrix metalloproteinase-9-1562C〉T polymorphism may increase the risk of lymphatic metastasis of colorectal cancer

AIM: To explore the role of the matrix metalloproteinase-9 (MMP-9) polymorphism in colorectal cancer (CRC) in a northeast Chinese population. METHODS: Genotyping of MMP-9 -1562C>T and 279R>Q polymorphisms was carried out on blood samples from 137 colorectal cancer patients and 199 controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multivariate logistic regression models were used to calculate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). RESULTS: The distribution of MMP-9 -1562C>T and 279 R>Q genotype was not significantly associated with the risk of CRC. However, the risk of llymph node metastasis of CRC was increased in patients with the -1562T allele (OR = 2.601; 95% CI = 1.160-5.835; P = 0.022). The frequency of MMP-9 279RR RQ genotype was higher than the QQ genotype among CRC patients younger than sixty years old (OR = 0.102; 95% CI = 0.013-0.812; P = 0.012). CONCLUSION: Our results indicated that the MMP-9-1562C>T polymorphism affects lymph node metastasis of CRC. In addition, the MMP-9 279R allele may lead to a younger age of onset of colorectal cancer.     

MMP-9基因启动子C1562T多态性与老年冠心病易感性的相关性研究

目的探讨基质金属蛋白酶9(MMP-9)基因启动子C1562T多态性与老年冠心病(CHD)易感性的相关性。方法纳入2009年3月~2012年12月北京航天总医院年龄≥60岁的CHD患者168例作为CHD组,纳入同期健康体检者208例作为对照组。取外周血标本提取DNA,采用聚合酶链式反应-限制性内切酶片段长度多态性(PCR-RFLP)方法检测MMP-9基因启动子C1562T基因型,比较两组间MMP-9基因多态性频率分布的差异。结果 MMP-9基因启动子区C1562T多态性基因型和等位基因频率分布在CHD组和对照组之间差异有统计学意义(P0.05)。CHD组1562T等位基因频率明显高于对照组(20.8%vs.13.0%,P=0.004),携带T等位基因个体患冠心病的风险是C等位基因的3.97倍(OR=3.97)。不同临床类型的CHD患者在基因型及等位基因分布方面的差异无统计学意义(P0.05)。结论 MMP-9基因C1562T多态性与老年CHD的发生有关联,T等位基因可能是冠心病发病的遗传易感基因。     

基质金属蛋白酶9基因多态性与2型糖尿病血管病变的相关性研究

目的 探讨基质金属蛋白酶9(MMP-9)基因C-1562T多态性与2型糖尿痫血管病变的关系．方法 运用PCR-RFLP检测110名健康对照者和450例2型糖尿病(DM)患者(其中单纯2型DM者100例、大血管病变者120例、糖尿病肾病(DN)患者130例、糖尿病视网膜病变患者100例)的MMP-9基因型，比较各组的基因型和等位基因频率。结果 (1)所有糖尿病视网膜病变患者的基因型均为CC型。(2)与对照组和单纯2型DM组相比，大血管病变组的T基因型和T等位基因频率显著升高，而DN组的TT基因型和T等位基因频率明显下降。(3)Logistic回归分析显示MMP-9 T等位基因、血清MMP-9、总胆固醇、低密度脂蛋白胆固醇、脂蛋白(a)是大血管病变发生的危险因素；尿白蛋白排泄率、脂蛋白(a)、HbA1C是DN发生的危险因素。结论 MMP-9基因C-1562T多态性与2型DM血管病变的发生有关，T等位基因是大血管病变的易感基因，是DN的保护基因。     

Expression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in recurrent chronic rhinosinusitis with nasal polyposis

Matrix metalloproteinase (MMP) is involved in the upper airway remodeling process. We hypothesized that MMP had an additive effect on the formation of recurrent nasal polyp. We also investigated the association between the functional promoter polymorphism of MMPs and the intensity of labeling index. Expressions of MMP-2 and MMP-9 were assessed via immunohistochemical staining and compared between different groups, including recurrent nasal polyps, nonrecurrent nasal polyps, and control nasal mucosa. Two promoter functional single-nucleotide polymorphisms (rs3918242 for MMP-9 and rs243865 for MMP-2) were selected to correlate with staining intensity. Expression of MMP-9 was significantly enhanced in gland for recurrent nasal polyp (p = 0.016) and nonrecurrent nasal polyp (p = 0.005) compared to the control. MMP-2 positivity was significantly increased in surface epithelium for recurrent nasal polyp (p = 0.004) compared to the control (p = 0.061). However, there was no significant difference in MMP-9 and MMP-2 expressions between recurrent and nonrecurrent nasal polyps. Genetic polymorphism of MMP-2 and MMP-9 functional promoters was not associated with the intensity of labeling index. These results suggested that up-regulation of MMP-9 in gland and MMP-2 in surface epithelium was characteristic of both recurrent and nonrecurrent nasal polyps. Pathogenesis of recurrent nasal polyps may involve a mechanism other than MMP.     

基质金属蛋白酶-9基因单核苷酸多态性与冠状动脉血管狭窄的相关性

目的研究我国河北省汉族人群基质金属蛋白酶-9(MMP-9)基因单核苷酸多态性-1562C>T与冠心病患者冠状动脉狭窄程度的相关性。方法收集经冠状动脉造影证实的冠心病患者91例和101例正常对照者,采用聚合酶链反应后直接测序的方式检测个体的基因型;比较不同基因型与血管狭窄的关系,并分析基因型与狭窄程度的关系。结果血管狭窄病例组和对照组MMP-9 C1562T C/C,C/T,T/T基因型分布频率无差异;C等位基因频率无显著差异;病例组之间各基因型和等位基因频率无显著性差异。结论 C1562T多态可能与冠心病的发生无关。     

基质金属蛋白酶9及其启动子C-1562T基因多态性与冠心病的相关性研究

目的探讨基质金属蛋白酶9（MMP-9）及其启动子C-1562T基因多态性在冠心病发病中的作用及其临床意义。方法入选163例患者,冠心病组103例,其中急性冠脉综合征（ACS）组71例,稳定型心绞痛（SAP）组32例;对照组60例。采用限制性内切酶片段长度多态性（PCR—RFLP）法鉴定MMP-9启动子C-1562T基因型,所有患者均行冠脉造影检查明确冠状动脉病变情况。结果①冠心病组MMP-9启动子-1562C／T基因型频率较对照组增高,-1562T型等位基因频率增高,差异有统计学意义。②冠心病患者MMP-9浓度较对照组明显升高,差异有统计学意义。③有T型等位基因患者MMP-9浓度较无T型等位基因患者升高,差异有统计学意义。④冠心病与其危险因素logistic回归分析提示,吸烟、高血压、高脂血症、肥胖、MMP-9启动子-1562T型等位基因为冠心病的危险因素。结论MMP-9启动子C-1562T基因多态性与冠心病的发病可能相关,T型等位基因可能是冠心病患者遗传易感性基因标志之一。MMP-9启动子C-1562T型等位基因可能引起MMP-9表达增高。     

Epistasis among eNOS, MMP-9 and VEGF maternal genotypes in hypertensive disorders of pregnancy

Polymorphisms of the endothelial nitric oxide synthase (eNOS), matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) genes were shown to be associated with hypertensive disorders of pregnancy. However, epistasis is suggested to be an important component of the genetic susceptibility to preeclampsia (PE). The aim of this study was to characterize the interactions among these genes in PE and gestational hypertension (GH). Seven clinically relevant polymorphisms of eNOS (T-786C, rs2070744, a variable number of tandem repeats in intron 4 and Glu298Asp, rs1799983), MMP-9 (C-1562T, rs3918242 and -90(CA)(13-25), rs2234681) and VEGF (C-2578A, rs699947 and G-634C, rs2010963) were genotyped by TaqMan allelic discrimination assays or PCR and fragment separation by electrophoresis in 122 patients with PE, 107 patients with GH and a control group of 102 normotensive pregnant (NP) women. A robust multifactor dimensionality reduction analysis was used to characterize gene-gene interactions. Although no significant genotype combinations were observed for the comparison between the GH and NP groups (P>0.05), the combination of MMP-9-1562CC with VEGF-634GG was more frequent in NP women than in women with PE (P<0.05). Moreover, the combination of MMP-9-1562CC with VEGF-634CC or MMP-9-1562CT with VEGF-634CC or-634GG was more frequent in women with PE than in NP women (P<0.05). These results are obscured when single polymorphisms in these genes are considered and suggest that specific genotype combinations of MMP-9 and VEGF contribute to PE susceptibility.     

血管紧张素转化酶及基质金属蛋白酶-9基因多态性与特发性肺纤维化的相关性研究

目的 分析特发性肺纤维化（IPF）患者血管紧张素转化酶（ACE）及基质金属蛋白酶-9（MMP-9）基因多态性与IPF的相关性.方法 选择120例我院就诊的IPF患者作为研究组,同时期健康体检者120例为对照组.应用PCR-RFLP技术对ACE基因16I/D与MMP-9基因1562C/T多态性位点进行基因分型,检测患者并比较血管紧张素转化酶（ACE）、血管紧张素Ⅱ（AngⅡ） 及MMP-9水平.以ACE 及MMP-9基因型作为自变量,以IPF为因变量进行风险因素分析.结果 与对照组相比,研究组的16DD/1562CC、16DD/1562CT、16DD/1562TT、16ID/1562CC基因型频率显著较高（P〈0.05）;ACE基因的D等位基因频率显著较高（P=0.026）,ACE基因的I等位基因、MMP-9基因的C及T等位基因频率无显著差别（P〉0.05）;研究组的ACE、AngⅡ水平显著较低,而MMP-9水平显著较高（P〈0.05）.仅16DD/1562CC基因型与IPF发病存在正相关关系（P=0.032）.结论 ACE与MMP-9的基因多态性与IPF的发病有相关性.     

急性冠脉综合征血清MMP-3水平及其基因启动子区域5A/6A多态

目的探讨基质金属蛋白酶-3（MMP-3）血清水平及其基因启动子区域5A/6A多态性与急性冠脉综合征（ACS）的关系。方法 ACS组135例,对照组71例。测定MMP-3血清水平,并对MMP-3启动子区域基因测序,分析其5A/6A多态性。结果 ACS组中AMI亚组的MMP-3血清水平高于对照组（P〈0.01）。MMP-3基因启动子区5A/6A单核苷酸多态性（SNP）的基因型在ACS组和对照组的分布有统计学差异（P〈0.05）,在ACS组中5A等位基因频率高于对照组（P〈0.05）。ACS组5A/5A基因型血清MMP-3浓度高于5A/6A基因型血清MMP-3浓度（P〈0.05）;ACS组5A/5A＋5A/6A基因型血清MMP-3浓度高于6A/6A基因型血清MMP-3浓度（P〈0.05）。进行多因子logistic回归分析,发现吸烟、高脂血症、糖尿病、高血压为ACS的主要危险因子,5A/5A＋5A/6A基因型（OR2.11,95%CI1.23～5.11,P〈0.01）亦是ACS发病的独立危险因子。吸烟并携带5A等位基因者较不吸烟携带6A/6A者有5倍的ACS发病风险（P〈0.01）。结论 MMP-3基因启动子区域5A/6A多态性及MMP-3循环水平升高与ACS发病密切相关;MMP-3血清水平受其基因5A/6A单核苷酸多态性的影响;吸烟与MMP-3基因5A/6A多态性对ACS具有协同的影响。     

基质金属蛋白酶-9基因C1562T多态性与高血压颈动脉粥样硬化关系

目的:研究基质金属蛋白酶-9(MMP-9)基因C1562T多态性与高血压颈动脉粥样硬化的相关性。方法:原发性高血压患者120例,测定受试者双侧颈动脉内-中膜厚度(IMT),IMT≥1.3mm认为存在粥样硬化斑块。依颈动脉有无粥样硬化分为颈动脉粥样硬化组、颈动脉正常组。用聚合酶链反应-限制性片段长度多态性分析法分析2组患者的MMP-9基因C1562T的多态性。结果:颈动脉粥样硬化组与颈动脉正常组CT TT基因型频率分别为28.8%、13.2%,差异有统计学意义(χ2=4.488,P=0.034),T等位基因与颈动脉粥样硬化发病密切相关(OR=2.092,95%CI:0.991~4.419,P=0.047)。结论:MMP-9T等位基因与高血压颈动脉粥样硬化密切相关,可能是其遗传标志。     

Prognostic impact of matrix metalloproteinase gene polymorphisms in patients with heart failure according to the aetiology of left ventricular systolic dysfunction.

AIMS: To assess the possible effect of functional polymorphisms in matrix metalloproteinase (MMP) gene promoters on the clinical outcome of patients with heart failure. METHODS AND RESULTS: We studied 444 consecutive patients who were referred to our centre for evaluation of left ventricular dysfunction. We extracted genomic DNA from white blood cells and determined the -1306 C >T MMP-2, -1171 5A > 6A MMP-3, and -1562 C >T MMP-9 polymorphisms. Clinical follow-up (median 717 days) was obtained for 443 patients. The MMP-3 polymorphism had a different impact on cardiac survival in HF patients with ischaemic and non-ischaemic cardiomyopathy (interaction p <0.03). The MMP-3 5A/5A genotype was an independent predictor of cardiac mortality (HR 2.92 [1.23-6.69]; p = 0.01) in patients with non-ischaemic HF. In contrast, there was no evidence for any effect of the MMP-3 genotype on cardiac events in patients with ischaemic cardiomyopathy. The MMP-9 polymorphism was associated with cardiac survival (p < 0.03) independently of HF aetiology. In multivariate analysis, the MMP-9 T allele was an independent predictor of cardiac mortality (HR 1.81 [1.09-3.02]; p = 0.02). Finally, there was no evidence for any association between MMP-2 polymorphism and cardiac survival. CONCLUSION: MMP-3 and MMP-9 polymorphisms contribute to variability in cardiac survival in HF patients. These data suggest that MMP genotyping could provide important additional information for refining risk stratification in patients with heart failure. MMP genotyping may help to select patients who could benefit from MMP inhibition.     

Association of matrix metalloproteinase-2 gene polymorphisms with susceptibility to type 2 diabetes: A case control study

AimsGenetic variations mediating MMP-2 expression may result in individual differences in susceptibility to particular diseases. Our aim was to investigate the possible association of certain MMP-2 gene variants with the susceptibility of type 2 diabetes (T2D) in a Tunisian population.Subjects and methodsA retrospective case-control study involving 310 normoglycemic control subjects and 791 T2D patients was conducted. Genotyping of MMP-2 variants was performed by real time PCR.ResultsMinor allele frequencies (MAF) of the rs243865 and the rs243866 MMP-2, were significantly different between T2D cases and controls. Setting homozygous wild-type genotype carrier as reference, a reduced risk of T2D was seen with the rs243865 and the rs243866 genotypes. Haploview analysis revealed limited linkage disequilibrium between the tested MMP-2 and variants, with most haplotypes (99.5%) captured by 7 MMP-2 haplotypes. Taking the GCCC haplotype as reference for MMP-2 (OR = 1.00), a reduced frequency of TTCC haplotypes (P = 0.04) and the GTCC haplotype (P = 3.5 · 10^?5) was noted in T2D which indicates a protective nature of these two haplotypes for T2D development.ConclusionTo the best of our knowledge, the present study is the first to demonstrate a consistent association of the rs243865 and rs243866 genotype with a protection for T2D.     

Association of MMP-2 genes variants with diabetic retinopathy in Tunisian population with type 2 diabetes

AimsFew studies investigated the association of genetic difference in metalloproteinase-2 (MMP-2) gene with diabetic retinopathy but with mixed outcome. To investigate the association between a set of MMP-2 genetic variants and the risk of diabetic retinopathy in an Arab Tunisian population with type 2 diabetes.Subjects and methodsA retrospective case-control study comprising a total of 779 type 2 diabetes patients with or without diabetic retinopathy was conducted. Genotyping was prepared by TaqMan® SNP genotyping qRT-PCR. The variants used were rs243865 (C/T), rs243864 (T/G), rs243866 (G/T) and rs2285053 (C/T).ResultsThe minor allele frequency (MAF) of the rs243864 MMP-2 variant was significantly higher among diabetic retinopathy patients. Setting homozygous wild type genotype carrier as reference, the rs243864T/G allele was associated with increased risk of diabetic retinopathy under the dominant, recessive, and additive models which persisted when key covariates were controlled for, while a reduced risk of diabetic retinopathy progression was seen after adjustment between non-proliferative and proliferative diabetic patients. Furthermore, the heterozygous genotype GT of the rs243866 variant is positively associated with the risk of proliferative diabetic retinopathy in the additive model. A limited linkage disequilibrium (LD) was revealed between the four-matrix metalloproteinase-2 variants. Four-loci haplotype analysis identified, GCTC, TTTC, and GCTT haplotypes to be positively associated with the risk of diabetic retinopathy.ConclusionOur findings demonstrate that the MMP-2 variant rs243864 and 243866 are related to the susceptibility to diabetic retinopathy and the progression of the disease in an Arab Tunisian population with type 2 diabetes.     

基质金属蛋白酶2基因多态性与缺血性收缩性心衰预后相关

目的基质金属蛋白酶家族（Matrix metalloproteinases,MMPs）是一组蛋白溶解酶系,在心肌细胞外基质降解过程中发挥重要作用。MMP-2作为家族中的重要成员,在心力衰竭心肌重构过程中起关键作用。我们推测MMP-2基因多态性可能会影响收缩性心衰的预后。方法对387位缺血性收缩性心衰患者进行随访,用限制性片段长度多态性的方法（restriction fragment length polymorphism,RFLP）分析MMP-2基因的三个单核苷酸多态性（single nucleotide polymorphisms,SNPs）位点rs243864,rs243866,rs17859821。结果随访到335位患者,随访率86．6％。在随访期间（0～47个月,中位随访时间24个月）,有72例（21．5％）患者死亡,56例（16．7％）患者因心衰再次入院,3例（0．9％）患者再次心肌梗塞,24例（7．2％）再次血运重建。1年、2年、3年的生存率分别是86％、79％、73％。MMP-2 rs17859821 A等位基因携带者全因死亡率、心源性死亡率、心衰死亡率和主要心脏不良事件率（major adveme cardiac event,MACE）均高于GG基因型者（OR=0．513,0．416,0．472,0．671;P=0．010,0．002,0．021,0．022）。使用Cox回归分析校正年龄、束支传导阻滞、LVEF和NYHA分级后,A等位基因携带者心源性死亡率和心衰死亡率仍显著或临界显著低于GG基因型者（OR=0．475,0．518;P=0．010,0．050）。结论研究结果提示携带MMP-2 rs17859821A等位基因的缺血陛收缩性心衰患者预后较好。     

Polymorphisms in the promoter regions of MMP-2, MMP-3, MMP-9 and MMP-12 genes as determinants of aneurysmal coronary artery disease

OBJECTIVES: Our hypothesis was that functional polymorphisms in matrix metalloproteinase (MMP) genes may act as susceptibility factors for the development of coronary aneurysms (CAs). BACKGROUND: Different forms of remodeling have been described at the level of coronary arteries; CA, reported in 1% to 5% of patients with angiographic evidence of coronary artery disease (CAD), are one of them. Matrix metalloproteinases have been implicated in the pathogenesis of aneurysm development through increased proteolysis of extracellular matrix proteins. METHODS: We screened 3,862 patients who underwent coronary angiography and identified 113 patients with CAD with at least one CA (CA group); these patients were matched with 226 patients with CAD without CA (control group). The -1,306 C/T MMP-2, 5A/6A MMP-3, CA-repeat MMP-9 and -82 A/G MMP-12 polymorphisms were determined. RESULTS: The MMP-2, MMP-9 and MMP-12 polymorphisms were not associated with CA. By contrast, the 5A/5A genotype of MMP-3 was significantly more frequent in the CA group than in the control group (31% vs. 18%, p = 0.015); similarly, the MMP-3 5A allele was more frequent in the CA group (p = 0.009). Three variables were independently associated with CA: the MMP-3 5A/5A genotype (odds ratio [OR] = 2.23, 95% confidence interval [CI] [1.27 to 3.93]), a previous myocardial infarction (OR = 1.91, 95% CI [1.14 to 3.20]) and a history of aortic aneurysm (OR = 21.06, 95% CI [2.35 to 188]). CONCLUSIONS: The MMP-3 5A allele is associated with the occurrence of CA. Our results suggest that an increased proteolysis in the arterial wall may act as a susceptibility factor for the development of CA in patients with coronary atherosclerosis.     

Genetic polymorphism in matrix metalloproteinase-9 and transforming growth factor-β1 and susceptibility to combined pulmonary fibrosis and emphysema in a Chinese population

In this study, we aimed to explore the association of genetic polymorphism in matrix metalloproteinase-9 (MMP-9) and transforming growth factor-β1 (TGF-β1) and the susceptibility to combined pulmonary fibrosis and emphysema (CPFE). We examined the polymorphisms of the MMP-9 C-1562T and TGF-β1 T869C in 38 CPFE patients, 50 pulmonary emphysema patients, and 34 idiopathic pulmonary fibrosis (IPF) patients. The frequencies of polymorphic genotypes in MMP-9 were 78.95% CC and 21.05% CT in CPFE group, 76.0% CC and 24.0% CT in emphysema group, and 100.0% CC in IPF group. There were highly statistically significant increased frequencies of the CT genotype and T allele in CPFE and emphysema groups compared with IPF group (p < 0.05). The frequencies of polymorphic genotypes in TGF-β1 were 2.63% CC, 28.95% CT, 68.42% TT in CPFE group, 4.00% CC, 16.00% CT, 80.00% TT in emphysema group, and 5.88% CC, 41.18% CT, 52.94% TT in IPF group. Significant increases in the TT genotype and T allele frequencies were observed in emphysema group compared with IPF group (p < 0.05). Our study has showed that T allele in MMP-9 (C-1562T) and T allele in TGF-β1 (T869C) are risk factors of pulmonary emphysema. The T allele in MMP-9 (C-1562T) possibly predisposes patients with pulmonary fibrosis to develop emphysema.     

MMP-8 C-799T and MMP-8 C+17G polymorphisms in mild and severe preeclampsia: Association between MMP-8 C-799T with susceptibility to severe preeclampsia

Objective: The aim of present study was to determine the role of matrix metalloproteinase-8 (MMP-8) C-799T (rs11225395) and C+17 (rs2155052) polymorphisms in susceptibility to preeclampsia. Study design: In a case–control study, 256 pregnant women including 152 women with preeclampsia (86 women with mild preeclampsia and 66 women with severe preeclampsia) and 104 women with normal pregnancy from Western Iran with Kurdish ethnic background were investigated for MMP-8 C-799T and C + 17G polymorphisms using polymerase chain reaction-restriction fragment length polymorphism method. Results: Comparing the MMP-8 TT genotype with the combined genotype of CC+CT (recessive model) indicated a significantly higher frequency of the MMP-8 TT genotype (47%) in severe preeclamptic patients than that in healthy pregnant women (30.8%) that was associated with 1.99-fold increased risk of severe preeclampsia (95% CI = 1.05–3.77, p = 0.034). The frequency of MMP-8 G allele was 27.3% in all preeclamptic patients compared to 30.2% in controls (p = 0.56). Also, no significant difference was detected comparing the frequency of G allele in mild (26.6%, p = 0.46) and severe preeclamptic patients (28.4%, p = 0.75) with controls (30.2%). Conclusions: Our study demonstrated that the MMP-8 C-799T is associated with the risk of developing severe preeclampsia during pregnancy. However, the MMP-8 C + 17G polymorphism might not be a risk factor for susceptibility to preeclampsia.