Association between the severity of angiographic coronary artery disease and paraoxonase-1 promoter gene polymorphism T[-107] C in Iranian population

The oxidation of low-density lipoproteins and cell membrane lipids is believed to play an integral role in the development of fatty streak lesions, an initial step in coronary artery disease [CAD]. Paraoxonase-1 [PON1] is an enzyme associated with the high-density lipoprotein [HDL] particle. PON1 protects LDL from oxidative modification by hydrolyzing lipid peroxides, suggestive of a role for PON1 in the development of CAD. The present study tested the hypothesis that Paraoxonase-1 promoter polymorphism T[-107]C could be a risk factor for severity of CAD in Iranian population. Paraoxonase-1 promoter genotypes were determined in 300 consecutive subjects [> 40 years old] who underwent coronary angiography [150 subjects with >50% stenosis served as cases [CAD+] and 150 subjects with < 20% stenosis served as controls [CAD-]]. PON1 promoter genotypes were determined by PCR and BSTU1 restriction enzyme digestion. CAD+ Subjects did not show any significant differences in the distribution of PON1 promoter genotypes as compared to CAD- Subjects [P = 0.075]. However the analysis of PON1 promoter genotypes distribution showed a higher percentage of [-107] TT among CAD+ compared with CAD- [P = 0.027]. After controlling for other risk factors, the T[- 107]C polymorphism had interaction with age [P = 0.012], but did not show any interaction with other risk factors such as BMI, gender, smoking, diabetes, level of HDL-C, LDL-C, triglyceride and Total cholesterol. These data suggest that the TT genotype may represent a genetic risk factor for Coronary artery disease in Iranian population

[Investigation of gelatinase- B enzyme role in invasion and metastasis of breast cancer]

Gelatinase B or collagenase type IV is a 92 kDa protein. In case of over-expression of the gene, because of its collagenase activity, it can be involved in metastasis activity of few cancers e.g. bladder, colorectal and gastric carcinoma. Single nucleotide substitution base polymorphism of C to T at -1562 of promotor region can increase gene expression by decreasing transcription inhibitor proteins binding at T alleles. The aim of this case-control study is to investigate the role of this polymorphism in development and invasion of breast cancer in Isfahan women population. At this study 90 breast cancer patients with metastasis and 100 healthy controls were analyzed using polymerase chain reaction-restriction fragment length polymorphism assay [PCR-RFLP]. The mean of follow up period was 2 years. Patients were checked every 3-5 months Data analysis showed a close association between the presence of T allele and invasion of breast cancer [OR = 5.85, 95% CI: 2.64-12.93, p <0.0001]. According to our findings, the major role of this polymorphism is in cancer cell metastasis and invasion of these cells to adjacent tissues