Cerebral stroke (CS) is the leading cause of death in China, and a complex disease caused by both alterable risk factors and genetic factors. This study intended to investigate the association of MMP3, MMP14, and MMP25 single nucleotide polymorphisms (SNPs) with CS risk in a Chinese Han population.
A total of 1,348 Han Chinese were recruited in this case-control study. Four candidate loci including rs520540 A/G and rs679620 T/C of MMP3, rs2236302 G/C of MMP14, and rs10431961 T/C of MMP25 were successfully screened. The correlation between the four SNPs and CS risk was assessed by logistic regression analysis. The results were analyzed by false-positive report probability (FPRP) for chance or significance. The interactions between four SNPs associated with CS risk were assessed by multifactor dimensionality reduction (MDR).
rs520540 A/G and rs679620 C/T SNP in MMP3 were associated with risk of CS in allele, codominant, dominant and log-additive models. Ischemic stroke risk were significantly lower in carriers with rs520540-A allele and rs679620-T allele than those with G/G or C/C genotypes. However, rs520540-A allele and rs679620-T allele were associated with higher risk of hemorrhagic stroke. Stratified analysis showed that these two SNPs were associated with reduced risk of CS in aged < 55 years, non-smoking and non-drinking participants, and rs679620 SNP also reduced CS risk in male participants. The levels of uric acid, high-density lipoprotein cholesterol, and eosinophil were different among patients with different genotypes of rs520540 and rs679620. No statistically significant association was found between MMP14 rs2236302 G/C or MMP25 rs10431961 T/C with CS even after stratification by stroke subtypes, age, gender as well as smoking and drinking conditions in all the genetic models.
MMP3 rs520540 A/G and rs679620 C/T polymorphisms were associated with CS risk in the Chinese Han population, which provides useful information for the prevention and diagnosis of CS.

Matrix metalloproteinases (MMPs) play an important role in matrix remodelling, as well as in tendon integrity. Due to overuse, athletes often develop chronic tendinopathies. If not treated, they lead to severe impairment, even complete tendon ruptures.
The main purpose of this study was to investigate whether three functional polymorphisms within the MMP3 gene are associated with increased risk of developing tendinopathies in high-level Croatian athletes.
We have recruited one hundred fifty-five (63 high-level athletes with diagnosed tendinopathies and 92 asymptomatic controls) unrelated Caucasians for this case-control genetic study. All participants were genotyped for three single nucleotide polymorphisms (SNP) within the MMP3 gene: rs591058 C/T, rs650108 A/G and rs679620 G/A using the pyrosequencing method.
The MMP3 rs650108 GG (P = 0.0074) and rs679620 AA (P = 0.0119) genotypes were significantly over-represented in cases compared with controls, while rs591058 TT (P = 0.0759), as well as haplotype variant T - G - A (P = 0.06), implicated that there is an indication of predisposition for tendinopathies.
These results support association between functional variants within the MMP3 gene and the risk of tendinopathies in high-level athletes. Further research is needed to replicate these results in a larger population.

OBJECTIVE: Lumbar disk herniation (LDH) is a complex condition based on lumbar disk degeneration (LDD). Previous studies have shown that genetic factors are highly associated with the severity and risk for LDH. This case-control study was aimed to evaluate the association between the matrix metalloproteinase (MMP)-3 gene rs591058 C/T polymorphism and LDH risk in a southern Chinese population.
METHODS: A total of 231 LDH patients and 312 healthy controls were recruited in this study. Genotyping was analyzed using a standard polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP).
RESULTS: It was observed that TT genotype or T allele carriers of the MMP-3 gene rs591058 C/T polymorphism was more likely associated with an increased risk for LDH. Subgroup analyses showed the following characteristics increased the risk for LDH: female sex; cigarette smoking; and alcohol consumption. Furthermore, individuals with high whole body vibration, bending/twisting, and lifting were associated with an increased risk for LDH.
CONCLUSIONS: Taken together, these data indicated that the MMP-3 gene rs591058 C/T polymorphism was associated with an increased risk for LDH. The MMP-3 gene rs591058 C/T polymorphism might serve as a clinical indicator and marker for LDH risk in the Chinese population.

OBJECTIVE: The goal of this study is to evaluate the association between MMP-2, 3, TIMP-2, 3 polymorphisms and risk of colorectal cancer (CRC) in a Chinese Han population.
METHODS: Eight single nucleotide polymorphisms (SNP) were genotyped in 505 CRC patients and 510 controls. The association between candidate SNPs and risk of CRC were evaluated using odds ratio (OR), 95% confidence interval (95% CI).
RESULTS: The minor allele frequency of rs1053605 in cases was significantly lower than controls (p = 0.005). The CT genotype frequency of rs1053605 in cases was significantly lower than those in controls, while the frequencies of rs4789936-CT and rs715572-AG genotype of in cases were significantly higher than those in controls (p < 0.05). Genetic model analysis showed that rs522616 was associated with decreased risk of CRC under recessive model (p = 0.041); rs1053605 was correlated with decreased risk of CRC under dominant (p = 0.012) and additive (p = 0.009) models; rs4789936 also has association with decreased risk of CRC under recessive model (p = 0.021); while rs715572 was associated with increased risk of CRC under dominant (p = 0.007) and additive (p = 0.011) models.
CONCLUSIONS: Our results shed new light on association between MMP and TIMP polymorphisms and CRC risk.

Chronic periodontitis (CP) is the common form of inflammatory oral disease. Matrix metalloproteinases (MMPs) play a pivotal role in the progression of CP by degrading gingival tissue and its remodelling. Here, we conducted a case-control study to investigate a possible association of single-nucleotide polymorphism of MMP genes and their interaction with CP in the Indian population. A total of 357 DNA samples of venous blood was isolated, of which 157 were identified as CP patients and 200 were healthy individuals. Genotyping of six MMP genes (MMP1, MMP3, MMP7, MMP8, MMP12 and MMP13) was done using polymerase chain reaction following Sanger\'s method of sequencing. Statistical analyses were performed by SPSS v16.0, R package (SNPassoc). Gene-gene interactions were evaluated by MDR 3.0.2. The frequency of 6A allele of MMP3 -11715A-6A gene polymorphisms (36%) and G allele of MMP8 +17G-C gene polymorphisms (34%) were higher in the CP population compared with the healthy population (19% and 24%, respectively). A significant association of T allele of MMP8 -799C-T gene promoter polymorphism was found with CP (OR = 2.95, 95%CI = 2.16 - 4.04, P < 0.0001). Genotypic frequency of MMP12 -82A-G polymorphism is associated with CP risk while its allelic distribution is not (OR = 1.32, 95%CI = 0.93 - 1.88, P = 0.129). Gene-gene interactions show the best cross validation consistency model, i.e. MMP1 -519A-G X MMP7 -181A-G X MMP8 -799C-T polymorphismswith a value of 9/10. This gene-gene interaction shows that the significant association of MMP8 -799C-T polymorphism with CP increased susceptibility. Allelic distribution of MMP8+17G-C and MMP3-11715A-6A polymorphisms revealed their protective role towards decreased risk of CP. MMP1 -519A-G and MMP7 -181A-G polymorphisms show combinatorial synergistic effect on CP risk.

BACKGROUND: Dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host response is influenced by genetic factors. Matrix metalloproteinases (MMPs) are enzymes that contribute to degradation and removal of collagen from extracellular matrix.
OBJECTIVE: This case-control study aimed to investigate the haplotypic combination of MMP polymorphism (rs1144393, rs1799750, rs3025058, and rs11225395) and implant loss.
METHODS: Two hundred nonsmokers subjects were matched by gender, age, implant number and position and divided in control group, 100 patients with one or more healthy implants, and test group, and 100 patients with one or more implant failures. Genomic DNA was extracted from saliva and genotypes were obtained by PCR-RFLP.
RESULTS: A significant association of rs1799750 (MMP-1) and rs11225395 (MMP-8) polymorphism on early implant loss was demonstrated (P ≤ 0.001). Global haplotype analysis indicated a significant difference between both groups (P < 0.0001). Haplotype T-A-GG-5A-C had a statistically significant risk effect, while haplotype C-A-G-6A-C andT-G-2G-5A-C had a protective effect in implant loss.
CONCLUSIONS: The results of this study showed that MMPs haplotype are a risk factor to early implant loss.

Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D3 . The patient presented with tender swelling and erythema of both auricles, and the antibody to type II collagen was detected. The biopsy specimen revealed a dense mixed cell infiltration over the auricular cartilage. We reviewed eight cases with the association of RP and psoriasis, and in all cases the clinical course of psoriasis did not correlate with that of RP. The severity of RP was mild in the majority of cases, and our case was unique in that the patient had no joint symptoms. Adalimumab treatment was effective for both RP and psoriasis. Fat-suppressed contrast-enhanced magnetic resonance imaging was beneficial, not only to demonstrate subclinical inflammation in the nasal septum, but also to subjectively assess the improvement of RP.

Genetic factors may play an important role in frozen shoulder etiology, which may involve matrix metalloproteinase-3 (MMP3) gene polymorphisms. In this study, we examined single nucleotide polymorphisms in MMP3 for their association with frozen shoulder susceptibility in a Chinese Han population. The rs591058, rs650108, and rs679620 polymorphisms in the MMP3 gene were genotyped in 112 subjects diagnosed as having frozen shoulder and in 143 healthy controls. rs650108 was found to be significantly associated with an increased risk of frozen shoulder. For other single nucleotide polymorphisms, no statistically significant associations with frozen shoulder were found. In conclusion, our data demonstrated that the MMP3 rs650108 variant was significantly associated with increased frozen shoulder susceptibility in a Chinese Han population.

METHODS: A case-control study was performed on 105 patients with idiopathic scoliosis (IS) and 210 unrelated gender-matched controls from Bulgarian population.
OBJECTIVE: Investigation of the association between common genetic polymorphisms of IL-6 and MMP3 genes and the etiology and progression of IS among Bulgarian patients.
BACKGROUND: The IL-6 and MMP3 genes have been considered as candidate genes of IS in Caucasian population.
METHODS: Molecular detection of the promoter polymorphisms of IL-6 and MMP3 was performed by polymerase chain reaction followed by restriction fragment length polymorphism. The statistical analysis was performed by χ test with a value of P < 0.05 as statistically significant. The combinatorial effect of the candidate genes was also examined.
RESULTS: This case-control study revealed statistically significant association between the IL-6 (rs1800795) functional polymorphism and susceptibility to IS (χ = 16.055; P < 0.0001). In addition, a significant association between IL-6 (rs1800795) and curve severity was detected (χ = 16.87; P < 0.0001). No genotype or allele of MMP3 (rs3025058) was found to be correlated to the onset or progression of IS (P > 0.05). One IL-6-MMP3 genotype combination was associated with the susceptibility to IS.
CONCLUSIONS: IL-6 gene could be considered as a susceptibility and modifying factor of IS. The identification of molecular markers with diagnostic and prognostic value could be useful for early detection of children at risk for the development of IS and for prognosis of the risk for a rapid deformity progression. That would facilitate the therapy decisions and early stage treatment of the patient with the least invasive procedures.
METHODS: 4.

OBJECTIVE: After 9/11/2001, some Fire Department of New York (FDNY) workers had excessive lung function decline. We hypothesized that early serum matrix metalloproteinases (MMP) expression predicts World Trade Center-Lung Injury (WTC-LI) years later.
METHODS: This is a nested case-control analysis of never-smoking male firefighters with normal pre-exposure Forced Expiratory Volume in one second (FEV1) who had serum drawn up to 155 days post 9/11/2001. Serum MMP-1, 2,3,7,8, 9, 12 and 13 were measured. Cases of WTC-LI (N = 70) were defined as having an FEV1 one standard deviation below the mean (FEV1 ≤ 77%) at subspecialty pulmonary evaluation (SPE) which was performed 32 months (IQR 21-53) post-9/11. Controls (N = 123) were randomly selected. We modeled MMP\'s ability as a predictor of cases status with logistic regression adjusted for time to blood draw, exposure intensity, weight gain and pre-9/11 FEV1.
RESULTS: Each log-increase in MMP-3 and MMP-12 showed reduced odds of developing WTC-LI by 73% and 54% respectively. MMP-3 and MMP-12 consistently clustered together in cases, controls, and the cohort. Increasing time to blood draw significantly and independently increased the risk of WTC-LI.
CONCLUSIONS: Elevated serum levels of MMP-3 and MMP-12 reduce the risk of developing WTC-LI. At any level of MMP-3 or 12, increased time to blood draw is associated with a diminished protective effect.