Arginase-1 Variants and the Risk of Familial Coronary Artery Disease in Subjects Originating from Pakistan.

BACKGROUND: Genetic polymorphisms in the human arginase-1 (ARG1) gene locus and their effects on cardiovascular disease have not been thoroughly elucidated. The aim of the present study was to investigate the association of the variant ARG1 alleles rs2781666 and rs2781667 with coronary artery disease (CAD). METHODS: ARG1 rs2781666G/T and rs2781667C/T polymorphisms were characterized in a case-control study consisting of 200 complex Pakistani families with CAD history. Heritability of susceptibility/variant alleles was investigated from parent-offspring trios in these families. Determination of serum liped levels was performed spectrophotometrically, while serum arginase-1 activity and the concentrations of nitric oxide metabolites were detected by enzyme colorimetric assay. Genotyping of the two polymorphic sites in the ARG1 gene was performed using polymerase chain reaction and restriction analysis. RESULTS: A significant increase in arginase-1 activity was observed in CAD patients compared with controls (p < 0.0001). Arginase-1 was negatively correlated with serum nitrite and nitrate (r = -0.8137 and r = -0.8444, respectively). There was a significant difference in distribution of genotypes for rs2781666 and rs2781667 polymorphisms between patients and controls (p < 0.001 for each). Similarly, the variant T allele at both loci showed a significant association with the disease compared with subjects free of CAD (p < 0.0001 for each). The transmission-disequilibrium test revealed a significant association of rs2781666 and rs2781667 polymorphisms with CAD (p < 0.0001 for each). CONCLUSION: This report is the first to describe arginase-1 activity and an association between ARG1 gene polymorphisms and familial CAD from Pakistan.

Variables associated with recurrence in breast cancer patients-the Shaukat Khanum Memorial experience.

From a cohort of female breast cancer patients registered at the Shaukat Khanum Memorial Cancer Hospital and Research Center, in Lahore, Pakistan, during the time period extending from December 1994 to December 2002, 700 subjects who were followed up in time, were selected. Those who presented with benign tumors, carcinoma in situ, or metastases were excluded from the analyses. Age, tumor size, nodal status, menopause, estrogen receptor (ER), and progesterone receptor (PR) status, at the time of presentation, were determined. Tumors were classified according to the TNM classification (American Joint Commission on Cancer (AJCC)-sixth edition), and subsequently, grouped into T1/T2 and T3/T4. Lymph nodes were categorized as N0 (node-negative) and N1, N2, and N3 combined (node-positive). The odds ratio (OR) for developing recurrence in T3/T4 versus T1/T2 was determined to be 2.06 (95% confidence interval (CI) 1.39-3.05, p < 0.001); the OR for node-positive relative to node-negative was found to be 2.54 (95 % CI 1.61-4.0, p < 0.001). Furthermore, the association between the odds of developing recurrence in ER-positive compared to ER-negative was represented by an OR of 0.61, (95 % CI 0.40-0.94 (p= 0.02)). These findings are consistent with the observations that ER-positive, node-negative, and T1/T2 lesions have a decreased risk of recurrence. Also, ER-positive patients may have a better response to hormonal treatment than those who are ER-negative.