Relationship between genomic damage and clinical features in dialysis patients.

Patients with end-stage renal disease display enhanced genomic damage. We investigated the presence of genomic damage in the peripheral lymphocytes by using the micronucleus (MN) test and the factors associated with the MN frequency in hemodialysis (HD) and peritoneal dialysis (PD) patients. We studied 121 dialysis patients (60 HD and 61 PD) and 129 age- and gender-matched healthy controls. The MN analysis, used as a biomarker of chromosomal/DNA damage, was performed in peripheral lymphocytes by the cytokinesis-block method. Univariate analysis showed a significantly higher MN frequency in all patients in comparison with the controls (7.6% ± 0.3% vs. 4.9% ± 0.2%, respectively, p<0.001). Significantly higher frequency of MN was observed in both HD and PD patients compared to controls (7.7% ± 0.5% vs. 4.9% ± 0.2%, p<0.001 and 7.5% ± 0.5% vs. 4.9% ± 0.2%, p<0.001, respectively). Multivariate analysis was performed, and it showed that the low-density lipoprotein level was the only independent determinant of increasing MN frequency in our patients (ß=0.16, t=2.172, p<0.05). There is no significant difference in terms of genomic damage between two dialysis modalities, which suggests that PD may not be a more reliable choice in terms of genomic damage.

DNA repair XRCC1 Arg399Gln polymorphism is associated with the risk of development of end-stage renal disease.

Patients with end-stage renal disease (ESRD) display enhanced genomic damage. DNA repair gene polymorphisms may affect DNA repair capacity and modulate susceptibility to ESRD. In this study, we aimed to determine the frequency of polymorphisms in two DNA repair enzyme genes, Xeroderma pigmentosum complementation group D (XPD) and X-ray cross-complementing group 1 (XRCC1), in patients with ESRD and to evaluate their association with ESRD development. By using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP), we genotyped four single nucleotide polymorphisms (SNPs) in XPD codons 312 and 751 and XRCC1 codons 194 and 399 in 136 dialysis patients (71 patients undergoing hemodialysis and 65 subjected to peritoneal dialysis) and 147 healthy controls. Patients having XRCC1 399 Arg/Gln (OR:1.98; 95% CI: 1.21-3.25, P = 0.007) or XRCC1-399 Gln/Gln (OR: 3.95; 95% CI: 1.45-10.76, P = 0.005) genotype had a significantly higher risk of ESRD than those with XRCC1 399 Arg/Arg genotype. We also found a significantly higher frequency of the XRCC1 399Gln allele in patients with ESRD than in controls, with OR = 2.03 (95% CI = 1.08-3.81, P = 0.03). We further investigated the potential combined effect of these DNA repair variants on the risk of ESRD development. It was found that combination of the Arg/Gln or Gln/Gln genotypes of XRCC1 Arg399Gln polymorphism with the two possible genotypes of XPD-Asp312Asn or with the Lys/Gln or Gln/Gln genotypes of XPD Lys751Gln was significantly associated with the development of ESRD. This is the first report showing an association between DNA repair gene polymorphisms and ESRD development, and suggests that XRCC1 Arg399Gln polymorphism may confer increased risk for the development of the disease. Further larger studies should be conducted to confirm these results.

Is sexual dysfunction in women with obstructive sleep apnea-hypopnea syndrome associated with the severity of the disease? A pilot study.

INTRODUCTION: Obstructive sleep apnea-hypopnea syndrome (OSAHS) may have a significant negative effect on sexual function. AIM: To evaluate female sexual function in women with OSAHS. METHODS: Twenty-six patients with OSAHS were evaluated in two groups according to apnea-hypopnea index as mild (5-15, Group I, N = 16) or moderate-severe (>or=15, Group II, N = 10). A third group (N = 10) of patients suspected of sleeping disorders other than OSAHS who also underwent polysomnographic studies served as the control group. All women were evaluated with a detailed sexual history including Female Sexual Function Index (FSFI) questionnaire and Beck Depression Inventory (BDI). Meanwhile, serum levels of estradiol, prolactin, total and free testosterone and dihydroepiandrostenedione-S were determined. MAIN OUTCOME MEASURES: FSFI, BDI, and serum hormonal levels. RESULTS: The mean ages and total FSFI scores of Group I, Group II and the control group were 46 +/- 7.1, 45 +/- 3.8, and 41 +/- 5.4 (P > 0.05); 24.7 +/- 5.3, 24.5 +/- 6.3, and 30.0 +/- 2.5 (P < 0.05), respectively. The mean FSFI domain scores were not statistically different between Groups I and II (P > 0.05) (desire, 3.18 +/- 1.2 vs. 2.92 +/- 1.6; arousal, 3.96 +/- 1.1 vs. 3.67 +/- 1.2; lubrication, 4.83 +/- 1.0 vs. 4.12 +/- 1.1; orgasm 4.0 +/- 1.1 vs. 5.15 +/- 2.9; satisfaction 3.96 +/- 1.1 vs. 4.05 +/- 1.4 pain; 4.84 +/- 1.2 vs. 4.65 +/- 1.3). However, the mean scores of desire (3.18 +/- 1.2 vs. 3.96 +/- 0.7), orgasm (4.0 +/- 1.1 vs. 5.0 +/- 1.1), and satisfaction (3.96 +/- 1.1 vs. 4.76 +/- 1.0) domains of Group I were significantly lower than the control group. Meanwhile, the mean scores of desire (2.92 +/- 1.6 vs. 3.96 +/- 0.7) and lubrication (4.12 +/- 1.1 vs. 5.22 +/- 0.9) domains were statistically different between Group II and the control group. The mean BDI scores of patients in Group I, Group II and the control group were 19.3 +/- 6.3, 20.2 +/- 6.6, and 11.0 +/- 7.1, respectively (P < 0.01). In addition, the mean levels of hormonal parameters were not significantly different from the control group (P > 0.05). CONCLUSIONS: OSAHS is associated with a significant decrease in female sexual function. However, severity of OSAHS is not related with the degree of female sexual dysfunction (FSD). This situation reveals that both organic and psychogenic issues are being involved in FSD related with OSAHS.