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.

Diabetes mellitus is a multifactorial metabolic disorder characterized by hyperglycemia. Apoptosis in beta cells has been observed in response to diverse stimuli, such as glucose, cytokines, free fatty acids, leptin, and sulfonylureas, leading to the activation of polyol, hexosamine, and diacylglycerol/protein kinase-C (DAG/PKC) pathways that mediate oxidative and nitrosative stress causing the release of different cytokines. Cytokines induce the expression of Fas and tumor necrosis factor-alpha (TNF-α) by activating the transcription factor, nuclear factor-κb, and signal transducer and activator of transcription 1 (STAT-1) in the β cells in the extrinsic pathway of apoptosis. Cytokines produced in beta cells also induce proapoptotic members of the intrinsic pathway of apoptosis. The genetic alterations in apoptosis signaling machinery and the pathogenesis of diabetes include Fas, FasL, Akt, caspases, calpain-10, and phosphatase and tensin homolog (Pten). The other gene products that are involved in diabetes are nitric oxide synthase-2 (NOS2), small ubiquitin-like modifier (SUMO), apolipoprotein CIII (ApoCIII), forkhead box protein O1 (FOXO1), and Kruppel-like zinc finger protein Gli-similar 3 (GLIS3). The gene products having antiapoptotic nature are Bcl-2 and Bcl-XL. Epigenetic mechanisms play an important role in type I and type II diabetes. Further studies on the apoptotic genes and gene products in diabetics may be helpful in pharmacogenomics and individualized treatment along with antioxidants targeting apoptosis in diabetes.

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.

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Coronary artery disease (CAD) is the major cause of morbidity and mortality. Diabetes is one of the powerful and independent risk factor for CAD. Hyperglycemia and hypercholesterolemia initiate the oxidative stress and complications like atherosclerosis which induces poor prognosis in diabetic CAD patients. The aim of the present study was to assess oxidative stress by comparing the levels of malondialdehyde and comet tail length in diabetic CAD patients, non-diabetic CAD patients and healthy controls. The study included 400 subjects of which 200 were healthy controls, 100 were diabetic CAD patients, and 100 were nondiabetic CAD patients. Fasting and postprandial glucose levels, glycosylated hemoglobin, serum lipid levels, malondialdehyde, and DNA damage were estimated in all subjects by using commercially available kits and standard protocols. FBS (185.60 ± 6.0 mg/dL), PPG (250 ± 7.06 mg/dL), HbA1c (10.65 ± 2.01 %), TC (280.72 ± 5.25 mg/dL), TG (195.11 ± 5.99 mg/dL), LDL (163.28 ± 5.68 mg/dL), MDA (9.74 ± 2.33 n moles/mL), and comet tail length (21.60 ± 5.69 μm) were significantly high in diabetic CAD patients (p < 0.05) compared to non-diabetic CAD patients and controls. Fasting and postprandial blood sugar levels significantly correlated with oxidative stress markers like MDA (r = 0.553, r = 0.557, p < 0.01) and comet tail length (r = 0.489, r = 0.626, p < 0.01) in diabetic CAD patients compared to nondiabetic CAD patients. Our study showed that diabetic CAD patients with increased levels of oxidative stress markers (MDA and DNA damage) might have the poor prognosis than nondiabetic CAD patients.