BackgroundExtracellular matrix degradation by matrix metalloproteinases (MMPs) is an important mechanism involved in tumor invasion and metastasis. Genetic variations of MMPs have shown association with multiple cancers. The present study is focused to elucidate the association of MMP-1, 3 and 9 genetic variants with respect to epidemiological and clinicopathological variables by haplotype, LD, MDR, survival in silico analyses among South Indian women.Material and methodsMMP3–1171 5A/6A and MMP9–1562 C/T SNPs were genotyped by Allele specific polymerase chain reaction and MMP1-1607 1G/2G polymorphism by restriction fragment length polymorphism assays respectively, in 300 BC patients and age-matched 300 healthy controls. Statistical analysis was performed using the SNPStats and SPSS software. Linkage disequilibrium and gene-gene interactions were performed using Haploview and MDR software respectively. Further, transcription factor binding sites in the promoter regions of SNPs under study were carried out using AliBaba2.1 software.ResultsWe have observed an increased frequency of 2G-allele of MMP1, 6A-allele of MMP3 and T-allele of MMP9 (p<0.05) respectively in BC subjects. The 2G-6A haplotype (minor alleles of MMP-1 and MMP-3 respectively) has shown an increased susceptibility to BC. Further, MMP polymorphisms were associated with the clinical characteristics of BC patients such as steroid hormone receptor status, lymph node involvement and metastasis. SNP combinations were in perfect LD in controls. MDR analysis revealed a positive interaction between the SNPs. 5-years survival rate and cox-regression analysis showed a significant association with clinicopathological variables.ConclusionOur results suggest that MMP1–1607 1G/2G, MMP3–1171 5A/6A and MMP9–1562 C/T gene polymorphisms have synergistic effect on breast cancer. The interactions of MMPs clinical risk factors such as lymph node involvement has shown a strong correlation and might influence the 5-years survival rate, suggesting their potential role in the breast carcinogenesis.

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Interleukin-6 (IL-6) a pleiotropic cytokine is a central mediator of inflammation in the pathogenesis of coronary artery disease (CAD). Our aim is to evaluate the serum levels of IL-6 and C-reactive protein (CRP) and to analyze the IL-6 polymorphism in CAD patients and to identify the first-degree relatives (FDRs) at risk of the disease in comparison with healthy controls. Estimation of IL-6 levels by enzyme-linked immunosorbent assay (ELISA) and CRP by latex reagent kit method, and genotyping of IL6 gene variants -174 (G>C) was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 600 subjects. IL-6 and CRP levels were significantly high in patients followed by FDRs compared to controls. The frequency of the IL-6 genotype was significantly different between cases, FDRs and controls and association of serum IL-6 levels with genotype found to be significant in CC genotype compared to GC and GG at p < 0.01 in CAD patients and FDRs, while there is no significant difference observed in controls. The study shows the importance of inflammation in the pathogenesis of CAD and predicts the risk of future coronary events in healthy asymptomatic FDRs.

Introduction: Proprotein convertase subtilisin/kexin type 9 (PCSK9) genetic polymorphisms play a significant role in cholesterol homeostasis. Therefore, we aimed to investigate the association of PCSK9 genetic variations NM_174936.3:c.137G>T (R46L, rs11591147) and NM_174936.3:c.1120G>T (D374Y, rs137852912), as well as promoter DNA methylation status, with mRNA expression and circulating serum protein levels in coronary artery disease (CAD) patients.Methods: The present study includes 300 CAD cases and 300 controls from South India. Biochemical assays were performed using commercially available kits. PCSK9 rs11591147 and rs137852912 polymorphisms were analyzed by the polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas promoter DNA methylation status and gene expression were determined using methylation specific PCR and quantitative PCR respectively. Results:The genotypic distribution of PCSK9 rs11591147 revealed that individuals with the TT-genotype and T-allele have a reduced risk for CAD. Furthermore, patients with the PCSK9 rs11591147 TT genotype have a significantly lower total cholesterol and low-density lipoprotein-cholesterol levels and also higher high-density lipoproteincholesterol levels than individuals with the GG genotype. Logistic regression analysis has shown that the GG and GT (p = 1.51 Â 10 -8 , p = 1.47 Â 10 -9 ) genotypes predicted the risk for CAD with an odds ratio of 5.8 and 7.3 respectively. In addition, individuals with the TT genotype were hypermethylated at promoter DNA of PCSK9, resulting in lower mRNA expression and circulating serum proteins than in individuals with the GG genotype. In silico analyses revealed that rs11591147 T-allele has protein destabilizing capacity.

The presence of the allele T of the SNP rs495392 of the Klotho gene is associated with a decrease in the odds of progression of atheromatosis in CKD patients.