The rad2 mutant of Schizosaccharomyces pombe is sensitive to UV irradiation and deficient in the repair of UV damage. In addition, it has a very high degree of chromosome loss and/or nondisjunction. We have cloned the rad2 gene and have shown it to be a member of the Saccharomyces cerevisiae RAD2/S. pombe rad13/human XPG family. Using degenerate PCR, we have cloned the human homolog of the rad2 gene. Human cDNA has 55% amino acid sequence identity to the rad2 gene and is able to complement the UV sensitivity of the rad2 null mutant. We have thus isolated a novel human gene which is likely to be involved both in controlling the fidelity of chromosome segregation and in the repair of UV-induced DNA damage. Its involvement in two fundamental processes for maintaining chromosomal integrity suggests that it is likely to be an important component of cancer avoidance mechanisms.

Cells mutated at the rad13 locus in the fission yeast, Schizosaccharomyces pombe are deficient in excision-repair of UV damage. We have cloned the S.pombe rad13 gene by its ability to complement the UV sensitivity of a rad13 mutant. The gene is not essential for cell proliferation. Sequence analysis of the cloned gene revealed an open reading-frame of 1113 amino acids with structural homology to the RAD2 gene of the distantly related Saccharomyces cerevisiae. The sequence similarity is confined to three domains, two close to the N-terminus of the encoded protein, the third being close to the C-terminus. The central region of about 500 amino acids shows little similarity between the two organisms. The first and third domains are also found in a related yet distinct pair of homologous S.pombe/S.cerevisiae DNA repair genes (rad2/YKL510), which have only a very short region between these two conserved domains. Using the polymerase chain reaction with degenerate primers, we have isolated fragments from a gene homologous to rad13/RAD2 from Aspergillus nidulans. These findings define new functional domains involved in excision-repair, as well as identifying a conserved family of genes related to RAD2.

BACKGROUNDThe role of adipocyte hormones in modulating insulin sensitivity and glucose tolerance are of increasing interest and importance in studies of type 2 diabetes mellitus. Recently a unique signaling molecule, resistin, has been proposed as playing a role in the pathogenesis of obesity-related insulin resistance, but its relevance to human diabetes remains uncertain. Therefore, we assessed the relationship between serum resistin concentrations and insulin resistance in lean, overweight and obese (OW/OB) non-diabetic and diabetic Saudi women.SUBJECTS AND METHODSWe measured fasting serum resistin levels in 44 diabetic women with a mean body mass index (BMI) of 31.82±4.35 kg/m2, 21 OW/OB non-diabetic women with a mean BMI 30.71±3.42 kg/m2 and in 24 lean women with a mean BMI of 23.33±1.24 kg/m2. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance formula derived from fasting insulin and glucose levels.RESULTSThe concentrations of fasting serum resistin showed significant differences among the three groups (P<0.001). Mean serum resistin concentrations increased from lean (11.59± 2.08) to OW/OB non-diabetic (16.29±2.29) to diabetic (19.42±3.60 ng/mL) women. Significantly higher levels of glucose (P<0.001) and values for the homeostasis model assessment ratio (HOMA-R) (P<0.01) occurred in the diabetic compared to the lean and OW/OB non-diabetic subjects. Furthermore, resistin correlated significantly and positively with hip circumferences (r=0.39, P=0.039), weight (r=0.51, P=0.005), insulin (r=0.40, P=0.033), HOMA-R (r=0.49, P=0.007) and glucose (r=0.39, P=0.038) in diabetic women. In OW/OB non-diabetic subjects, resistin correlated with insulin (r=0.59, P=0.015) and HOMA-R (r=0.616, P=0.011). No correlation was observed with glucose, height, hip, waist, weight, and waist-hip ratio (WHR) in the lean and OW/OB non-diabetic groups.CONCLUSIONResistin concentrations are elevated in patients with type 2 diabetes and are associated with obesity and insulin resistance. These data indicate that resistin might be involved in the development of diabetes in humans.

Abstract. In order to evaluate the contribution of polymorphisms of the adiponectin gene, ADIPOQ, to the risk of colon cancer, we conducted a case-control study of 60 colon cancer patients and 60 age, gender and ethnicity-matched controls in the Saudi population. We tested the hypothesis by analyzing the genotypes for two single nucleotide polymorphisms (SNPs), rs1501299 (G276T) and rs2241766 (T45G), in the ADIPOQ gene. In addition, the study was also designed to assess whether the two SNPs contribute to circulating adiponectin levels. We observed an increased risk of colon cancer associated with the 276T allele. The odds ratio (OR) was 2.64 [95% confidence interval (CI), 0.49-14.6]. The G allele at the T45G polymorphism was associated with a lower risk of colon cancer (OR=0.41; 95% CI, 0.19-0.86). Our results suggest that the risk of developing colon cancer may be partially explained by genetic polymorphisms in the ADIPOQ gene.

BACKGROUND AND OBJECTIVESResistin is an adipocytokine, which has been studied for its role in insulin resistance and recently in inflammation. Several single-nucleotide polymorphisms (SNPs) have been identified in the human resistin gene (RETN). This study aims to investigate the association of RETN rs1862513 (C-420G) and rs3745367 (G+299A) SNPs with the colon cancer risk in Saudi patients.DESIGN AND SETTINGSThis is a case-control study conducted among Saudi adult colon cancer patients recruited from King Abdulaziz Hospital and Oncology Center in Jeddah, Saudi Arabia.SUBJECTS AND METHODSIn this study, 120 Saudi volunteers (60 colon cancer patients and 60 disease-free controls) were studied. The SNPs were determined by polymerase chain reaction (PCR) and genotyping using PCR- restriction fragment length polymorphism analysis.RESULTSIn comparing the result obtained for the patient group with that of the controls, colon cancer group displayed different genotype distribution of the RETN C-420G and G+299A SNPs. The study indicated that the SNP-420 heterozygous (CG) genotype (odds ratio [OR]=2.48, 95% CI 1.07–5.74, P=.03) and the SNP +299 heterozygous (GA) genotype (OR=6.5, 95% CI 1.77–24.18, P=.002) significantly increased the risk of colon cancer. A further analysis of the genotype combination of SNPs RETN C-420G and G+299A showed a larger increase in the colon cancer risk.CONCLUSIONThese preliminary results suggested a potential role for RETN C-420G and G+299A polymorphisms in the genetic predisposition to colon cancer disease.