Correlations of a disintegrin and metalloproteinase with thrombospondin type 1 motifs gene polymorphisms with vulnerability of carotid plaque and lipid-loweringing efficacy of atorvastatin in patients with cerebral infarction / 中华神经医学杂志

Objective To investigate the associations ofa disintegrin and metalloproteinase with thrombospondin type 1 motifs (ADAMTS1) gene single nucleotide polymorphism (SNPs) with vulnerability of carotid plaque formation and atorvastatin lipid-efficacy in patients with cerebral infarction.Methods Seven hundred and seventy-eight patients with anterior circulation infarction,admitted to our hospital from June 2010 to June 2015,were divided into the following 3 groups according to their carotid ultrasound examination results:vulnerable plaque group (n=291),stable plaque group (n=286) and no plaque group (n=201).Atorvastatin was given in patients from the 3 groups and the low density lipoprotein cholesterin (LDL-C) level was detected to evaluate the atorvastatin lipid-efficacy in 151 patients from vulnerable plaque group 4 weeks after treatment.The SNPs of rs402007 (G/C) in ADAMTS1 gene of all patients were detected by PCR amplification and DNA sequencing.Results There were statistically significant differences in age,fibrinogen (FIB) level,homocysteine (HCY) level and percentage of patients having diabetes among the three groups (P＜0.05).The frequencies of GC+CC genotype and C allele in rs402007 (G/C) ofADAMTS1 gene in the vulnerable plaque group were significantly higher as compared with those in the no plaque and vulnerable plaque groups (P＜0.05).After adjusting risk factors (age,FIB,HCY and diabetes),GC+CC genotype was the independent risk factor of vulnerable plaque (OR=1.559,P=0.015,95％CI:1.089-2.232).There were no significant differences in LDL-C levels before and after atorvastatin treatment among the GG,GC,and CC genotypes in vulnerable plaque group (P＞0.05).Conclusion C allele in ADAMTS1 gene might increase the risk of plaque's instability;no correlation exists between A DAMTS1 gene polymorphisms and LDL-C lowing efficacy to atorvastatin.

Association of ADAMTS-1 gene polymorphisms with ischemic stroke caused by large artery atherosclerosis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association of a disintegrin and metallo-proteinase with thrombospondin type 1 motifs (ADAMTS-1) gene polymorphism and ischemic stroke caused by large artery atherosclerosis (LAA).</p><p><b>METHODS</b>In total 767 patients and 506 controls were recruited. Single nucleotide polymorphisms (SNPs) rs416905 (T/C) and rs402007 (G/C) of the ADAMTS-1 gene were genotyped by polymerase chain reaction and DNA sequencing.</p><p><b>RESULTS</b>Frequencies of the rs402007 GC+CC genotype and the C allele were significantly different between the two groups (68.84% vs. 60.67%, χ2=9.012, P=0.003, OR=1.432; 45.24% vs. 38.54%, χ2=11.208, P=0.001, OR=1.318). Binary logistic regression has confirmed that the above difference was significant (P=0.001, OR=1.521, 95%CI: 1.183-1.955). The frequencies of TC+CC and GC+CC genotypes were similar between the two groups, and so was it with the C allele. The two SNPs had been in complete linkage disequilibrium (D'=1.0, r2=1.0).</p><p><b>CONCLUSION</b>The rs416905 and rs402007 polymorphisms of the ADAMTS-1 gene may be associated with ischemic stroke caused by LAA. The C allele of the rs402007 locus may be a susceptibility factor for this subtype of stroke.</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>