Association of MMP-14 gene polymorphism with cerebral infarction - a case-control study / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association between cerebral infarction (CI) and single nucleotide polymorphism (SNP) in the exon of membrane-type 1 matrix metalloproteinase (MMP-14) gene in Chinese Han population.</p><p><b>METHODS</b>Five hundred seventy four patients with CI and 463 healthy individuals were recruited. Serum MMP-14 level was measured with enzyme-linked immunosorbent assay (ELISA). rs1042704 and rs2236307 polymorphisms of the MMP-14 gene were genotyped with a TaqMan assay. Multivariate logistic regression was carried out to analyze the risk factors of CI.</p><p><b>RESULTS</b>A significant lower risk of CI was found in individuals with MMP-14 rs2236307 TC and CC genotypes (vs. TT genotype: P<0.05). The frequencies of MMP-14 rs2236307 C allele were significantly different between the CI group (37.46%) and the control group (43.95%) (P=0.003). Serum level of MMP-14 was higher in the CI group (P=0.003) and was also higher in the group with MMP-14 rs2236307 TT genotype compared with those with CT and CC genotypes (P=0.000; P=0.009). Logistic regression analysis indicated that the MMP-14 rs2236307 CT+CC genotypes was a protective factor, and that history of hypertension, smoking status, triglycerides, diastolic blood pressure and systolic blood pressure were the independent risk factors of CI (AOR:2.027, 1.302, 1.296, 1.434, 2.087; P<0.05).</p><p><b>CONCLUSION</b>The rs2236307 polymorphism of MMP-14 gene is associated with CI, for which the C allele maybe a protective factor. No association of MMP-14 gene rs1042704 polymorphism with CI has been found.</p>

Association between -1296T/C and -915A/G polymorphisms of matrix metalloproteinase inhibitor-3 gene and atherosclerotic cerebral infarction in an ethnic Han Chinese population / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between -1296T/C and -915A/G polymorphisms in the promoter region of matrix metalloproteinase inhibitor-3 gene (TIMP-3) and atherosclerotic cerebral infarction in an ethnic Han Chinese population.</p><p><b>METHODS</b>Peripheral blood samples were collected from 485 patients with atherosclerotic cerebral infarction and 525 healthy controls. Serum levels of TIMP-3 were measured with an enzyme-linked immunosorbent assay (ELISA). The polymorphisms of the TIMP-3 gene were analyzed with DNA sequencing.</p><p><b>RESULTS</b>There were significant differences in genotype and allele frequencies in -1296T/C and -915A/G between the patients and healthy controls (chi-square: 5.227 and 5.869; P: 0.022 and 0.015, respectively). Besides, there was a strong linkage disequilibrium between -1296T/C and -915A/G (D'=1.0, r(2)=0.991). The serum levels of TIMP-3 in patients were significantly higher than the control group [(248.90 ± 97.10) pg/mL vs. (200.17 ± 79.70) pg/mL, t=2.098, P=0.039].</p><p><b>CONCLUSION</b>The -1296T/C and -915A/G polymorphisms of the TIMP-3 gene are associated with increased risk for atherosclerotic cerebral infarction in ethnic Han Chinese and may be used as molecular markers for the disease. There is also strong linkage disequilibrium between the two loci.</p>

Association of serum levels of matrix metalloproteinase-12 and a functional polymorphism in the promoter-82A/G of the matrix metaiioproteinase-12 gene with acute atherosclerotic cerebral infarction / 中华神经科杂志

Objective To investigate the association of serum levels of matrix metalloproteinase-12 (MMP-12) and a functional polymorphism in the promoter - 82A/G of the MMP-12 gene with acute atherosclerotic cerebral infarction (ACI).Methods All 608 cascs of acute ACI and 374 healthy controls were included in the study.Serum levels of MMP-12 were measured using the enzyme-linked immunosorbent assay (ELISA). At the same time,polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed on the - 82A/G polymorphism in the MMP-12 gene.Results The serum levels of MMP-12 in ACI group (( 17.36 ± 9.12) ng/ml) were not significantly higher than those in the healthy control group ( ( 17.42 ± 7.70) ng/ml,t ＝ 0.047,P =0.962).The frequency of the AG + GG genotypes was not significantly different between the two groups (7.6％ vs 5.9％,x2 =0.281,P =0.584),and the frequencies of the G allele were 3.8％ and 2.9％ in the ACI group and the control group respectively which were also not significantly different between the two groups ( x2 =0.746,P =0.374).Conclusion There is no correlation between serum level with genetic polymorphism in MMP-12 promoter (-82A/G) and cerebral infarction.

Influence of plasma matrix metalloproteinase-7 levels and genetic polymorphism of -181A/G on the stability of carotid plaque / 中华神经科杂志

Objective To explore the influence of plasma matrix metalloproteinase-7 ( MMP-7 ) levels and genetic polymorphism of MMP-7 - 181 A/G on the stability of carotid plaque.Method According to carotid ultrasound examination, 503 patients with carotid atherosclerotic lesions were consecutively recruited and divided into vulnerable plaque group (n = 118) and stable plaque group (n = 385).Plasma MMP-7 levels were measured by enzyme-linked immunosorbent assay (ELISA), and MMP-7 -181 A/G genotypes were determined by polymerase chain reaction-restiction fragment length polymorphism (PCR-RFLP).Results Plasma MMP-7 levels in carotid vulnerable plaque group were significantly enhanced as compared to stable plaque group (t =5.49, P =0.00).The frequency of MMP-7 -181G allele in vulnerable plaque group was significantly higher than that in stable plaque group (11.4% vs 7.0% ,χ2 = 4.78, P= 0.029).Compared to AA genotype, the genotypes with - 181G allele (AG + GG) significantly increased susceptibility to carotid vulnerable plaque ( χ2 = 5.01, OR = 1.81, P = 0.025 ) .When further analyzing the relationship between genotype and plasma MMP-7 levels, no significant differences of plasma MMP-7 levels were observed between AA genotype and AG + GG genotype in stable plaque group.However, in vulnerable plaque group, plasma MMP-7 levels of AG + GG genotype were significantly higher than that of AA genotype( t = 2.62, P = 0.01).Conclusion The present findings suggest that plasma MMP-7 level may be a biomarker for carotid vulnerable plaque.Genetic polymorphism of - 181 A/G in MMP-7 promoter may affect the expression of MMP-7, and seems to be implicated in susceptibility to carotid vulnerable plaque.