Association between polymorphisms in osteopontin gene (SPP1) and first episode calcium oxalate urolithiasis.

We examined whether single nucleotide polymorphisms (SNPs) in SPP1 gene are associated with risk of calcium oxalate urolithiasis (COU). We genotyped nine known SNPs in SPP1 gene (rs11739060, rs28357094, rs2728127, rs11730582, rs1126772, rs9138, rs2853744, rs4754=p.Asp80Asp, and rs1126616=p.Ala236Ala). Genomic DNA from 1,026 individuals (n = 342 patients with first episode COU, and n = 684 healthy unrelated controls) was analyzed for nine SPP1 SNPs using polymerase chain reaction and melting curve analysis by means of a pair of fluorescence resonance energy transfer probes. Serum and urine osteopontin (OPN) levels were also measured using enzyme-linked immunosorbent assay kits. rs9138 AA genotype was protective (OR 0.62, 95 % CI 0.47-0.81; P = 0.004). rs28357094 TT genotype (OR 2.52, 95 % CI 1.74-3.79; P = 0.021), rs2728127 GG genotype (OR 2.64, 95 % CI 1.42-4.81; P = 0.002), and rs2853744 GG genotype (OR 1.68, 95 % CI 1.22-3.87; P = 0.003) were predisposing. None of the other examined SPP1 SNPs was associated with COU susceptibility. Subjects with protective and predisposing polymorphisms had increased and decreased serum levels of OPN, respectively. Urinary calcium/OPN ratios were higher and lower in subjects with predisposing and protective SNPs of SPP1 gene, respectively. Of 28 constructed haplotypes, 6 demonstrated significant association with COU risk. There was no sex difference in the obtained results. The SPP1 gene polymorphisms are associated with the COU susceptibility.

Association of genetic polymorphism of glutathione S-transferase (GSTM1, GSTT1, GSTP1) with bladder cancer susceptibility.

The glutathione-S-transferases (GSTs) comprise a class of enzymes that detoxify carcinogenic compounds by conjugating glutathione to facilitate their removal. Polymorphisms in GSTM1, GSTT1, and GSTP1 genes have been related to risk for bladder cancer. Studies focusing on GSTs gene variants relationship with the risk of bladder cancer have produced conflicting and inconsistent results. We examine the association between genetic polymorphism of glutathione S-transferase P1, GSTM1, GSTT1 genes and development of bladder transitional cell carcinoma (TCC). The study population consisted of 166 histologically confirmed male bladder TCC cases and 332 healthy male controls. Genotyping was done using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) method and also investigated combined gene interactions. The GSTP1 Val/Val genotype was significantly associated with bladder cancer (OR = 4.32, 95% CI: 2.64-6.34), whereas the association observed for GSTM1 null (OR = 1.32, 95% CI: 0.82-2.62; P = 0.67) and GSTT1 null genotype (OR = 1.18, 95% CI: 0.79-1.67; P = 0.74) did not reach statistical significance. There was a significant multiple interaction between GSTM1, GSTT1, and GSTP1 genotypes in risk of bladder cancer (P for interaction = 0.02). The risk associated with the concurrent presence of GSTM1 positive and GSTP1 Ile/Val or Val/Val (OR = 3.71, 95% CI: 2.34-5.54) and GSTT1 positive and GSTP1 Ile/Val or Val/Val (OR = 2.66, 95% CI: 1.54-4.72) was statistically significant. Patients carrying GSTP1 Val/Val genotype were at increased risk for developing high-grade (OR = 7.68, 95% CI: 4.73-19.25) and muscle invasive (OR = 10.67, 95% CI: 6.34-21.75) bladder cancer. High risk for bladder TCC also was observed with respect to combined GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 4.76, 95% CI: 2.68-18.72) and GSTM1 null/GSTT1 null/GSTP1 Ile/Val or Val/Val (OR = 6.42, 95% CI: 4.76-14.72) genotype variant. This study suggests that the GSTP1 polymorphism and its combination with GSTM1, and GSTT1 may be associated with bladder cancer susceptibility in the Iranian population. Further confirmation in large population-based studies is needed.

G-protein ß3 subunit gene 825C/T polymorphism and its association with the presence, severity, and duration of vasculogenic erectile dysfunction.

OBJECTIVE: To investigate the association between G-protein ß3 (GNB3) subunit gene 825C/T polymorphism and vasculogenic ED (VED). DESIGN: Case-control study. SETTING: Private urology and andrology clinic. PATIENT(S): The study included 246 patients with VED and 492 healthy controls, Caucasians of Iranian descent. INTERVENTION(S): Typing of the polymorphism was performed using the polymerase chain reaction restriction fragment length polymorphism technique. MAIN OUTCOME MEASURE(S): To test the hypothesis of whether the presence of the 825T allele of the GNB3 gene is associated with an increased risk of VED. RESULT(S): The CT genotype was more prevalent in VED patients relative to healthy controls (adjusted odds ratio [OR] = 2.34; 95% confidence interval [CI], 1.10-4.26). Interaction between T allele carriership and VED was significant. The dominant model CT + TT variant was associated with a 3.74-fold increase in the adjusted risk (OR = 3.74; 95% CI, 1.11-12.4) for the occurrence of VED. Our results indicate that the GNB3 polymorphism is associated with higher systolic blood pressure, higher dyslipidemia, and higher body mass index. The 825TT genotype was associated with a more than five-fold increased risk of severe VED compared with the 825CC genotype (OR = 5.62; 95% CI, 3.54-9.25). Significantly different onset of age of VED was not found between the genotypes for the GNB3 polymorphism. CONCLUSION(S): The GNB3 polymorphism is an independent risk factor for VED in Iranian males. Our findings confirm a role of GNB3 in the genetic susceptibility of VED and suggest that GNB3 polymorphism should be taken into consideration to improve the assessment of an individual's risk of VED.

Quality of life and sexual functioning in young women with early-stage breast cancer 1 year after lumpectomy.

BACKGROUND: The breast cancer (BC) and its treatment (mastectomy, radiotherapy, and chemotherapy) have considerable psychosexual impacts on women's life. This study evaluated sexual functioning, quality of life, and self-esteem in young women with early-stage BC. METHODS: A total of 186 women with stage I or II BC and 204 age-matched controls aged 25-45 years were recruited. To be eligible, patients had to be disease-free and sexually active. They also had to have undergone lumpectomy at least 1 year previously and have completed chemotherapy and/or radiotherapy. Subjects completed Female Sexual Function Index, Short Form-36 Health Survey, and Rosenberg Self-Esteem questionnaire. Serum sex hormones were also measured in all subjects. RESULTS: Of BC patients, 57% experienced lubrication disorder followed by satisfaction disorder in 53.8%, desire disorder in 42.5%, and arousal disorder in 37.0% (all patients vs. healthy controls <0.01). Hormone-treated patients were more likely to report sexual dysfunctions (p = 0.006). The radiotherapy + chemotherapy + hormone therapy was associated with an about sixfold increased risk of lubrication and satisfaction disorders (adjusted odds ratios = 6.4, 95%CI = 4.6-12.6, and adjusted odds ratios = 5.7, 95%CI = 3.4-11.4, respectively). Cancer patients had lower scores for all components of the Short Form-36 Health Survey, except for pain. Levels of self-esteem did not differ significantly between the two groups. CONCLUSIONS: Young lumpectomized BC women reported a marked impairment in sexual functioning and quality of life.

The influence of promoter -202 A/C polymorphism (rs2854744) of the IGFBP-3 gene on erectile dysfunction risk and serum levels of IGF-I and IGFBP-3.

PURPOSE: We studied whether the IGFBP-3 gene polymorphism rs2854744 is associated with erectile dysfunction. MATERIALS AND METHODS: We investigated the association of this polymorphism with erectile dysfunction in 176 cases and 352 controls. We genotyped rs2854744 using polymerase chain reaction-restriction fragment length polymorphism. Circulating concentrations of IGF-I and IGFBP-3 were also measured. RESULTS: Allelic frequencies were 0.474 (A allele) and 0.526 (C allele) in men with erectile dysfunction, and 0.457 (A allele) and 0.543 (C allele) in normal controls (adjusted OR 1.74, 95% CI 0.82-2.43, p = 0.08). The frequency of the IGFBP-3 A-202C polymorphism genotype was 0.273 (CC), 0.506 (AC) and 0.221 (AA) in the case group, and 0.296 (CC), 0.494 (AC) and 0.210 (AA) in the control group (chi-square test p = 0.08). Neither the IGFBP-3 A-202C polymorphism nor serum IGF-I and IGFBP-3 levels were significantly associated with the risk of erectile dysfunction. Carriers of the AA genotype had the highest age adjusted serum IGFBP-3. This demonstrated a stepwise decrease in the presence of 1 or 2 copies of the C allele (mean ± SD 4,541 ± 796.2, 3,552 ± 642.4 and 3,314 ± 669.3 ng/ml, respectively). There was a positive correlation between serum IGFBP-3 and serum IGF-I concentrations (Spearman correlation coefficient r = 0.34, p for trend = 0.001). CONCLUSIONS: The IGFBP-3 gene A-202C polymorphism does not modulate the risk of erectile dysfunction.

Effects of EPA, γ-linolenic acid or coenzyme Q10 on serum prostate-specific antigen levels: a randomised, double-blind trial.

The main objective of the present study was to determine the potential of n-3 and n-6 fatty acids or coenzyme Q10 (CoQ10) to alter serum prostate-specific antigen (PSA) levels in normal healthy men. A total of 504 healthy men with serum PSA level ≤ 2·5 ng/ml were recruited into the study. Serum PSA values were not segregated by decade of age. Participants were randomly assigned to a daily dietary supplement containing n-3 fatty acids (1·12 g of EPA and 0·72 g of DHA per capsule) (group 1, n 126), n-6 fatty acid (600 mg γ-linolenic acid (GLA) each capsule) (group 2, n 126), CoQ10 (100 mg per capsule) (group 3, n 126) or a similar regimen of placebo (group 4, n 126) for 12 weeks. Study medication was administered as two capsules to be taken twice daily. Serum levels of PSA, EPA, DHA, GLA, lipid profile and reproductive hormones were also measured. EPA treatment significantly reduced serum PSA level by 30·0 (95 % CI 25, 36) % (P= 0·004) from baseline. In contrast, GLA therapy significantly increased serum PSA concentration by 15·0 (95 % CI 11, 20) % (P= 0·02). CoQ10 therapy also significantly reduced serum PSA level by 33·0 (95 % CI 27, 40) % (P= 0·002). In multivariable analysis, serum values of PSA were strongly correlated with duration of EPA (r - 0·62; 95 % CI - 0·42, - 0·77; P= 0·003), n-6 (r 0·42; 95 % CI 0·31, 0·58; P= 0·02) and CoQ10 use (r - 0·77; 95 % CI - 0·56, - 0·87; P= 0·001). There were also significant correlations between serum values of DHA, EPA, GLA and CoQ10 and serum PSA levels. The present study demonstrates that dietary supplements containing EPA, GLA or CoQ10 may significantly affect serum PSA levels.

Effects of the T-786C, G894T, and Intron 4 VNTR (4a/b) polymorphisms of the endothelial nitric oxide synthase gene on the risk of prostate cancer.

Several studies have shown that nitric oxide (NO) and nitric oxide synthase (NOS) system plays an important role in carcinogenesis. Endothelial nitric oxide synthase (eNOS) gene polymorphisms significantly affects serum NO concentrations. Studies addressing the relationship between eNOS gene polymorphisms and prostate cancer (CaP) are very scarce. We examined the association between the 3 eNOS gene polymorphisms (T-786C, G894T, and 4a/b) with risk and clinical features of CaP. One hundred seventy patients with CaP (mean age 63.6 ± 12.4 years) and 340 age-matched healthy controls (mean age 64.9 ± 12.9 years) were recruited in this case-control study. Genotyping was performed by polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique. For T-786C polymorphism, we found that CC genotype was associated to CaP risk [odds ratio (OR) = 3.62, 95% confidence interval (CI): 1.89-7.74, P = 0.002), high grade tumor (OR = 2.46, 95% CI:1.78-4.72; P = 0.006), and advanced disease (OR = 4.67, 95% CI: 2.64-8.61; P = 0.002). Neither the CaP risk nor clinical features of CaP were associated with the G894T polymorphism. It was found that, compared with 4a/b bb genotype, the 4a/b "a" variant genotypes were associated with an increased risk of CaP in an allele dose dependent manner (OR = 2.12, 95% CI: 1.68-3.44; P = 0.031 for 4a/b ab genotype, and OR = 4.32, 95% CI: 2.21-6.08; P = 0.001 for 4a/b aa genotype). In addition, genotypes with the "a" allele of the eNOS 4a/b polymorphism predispose the patients to high grade (OR = 4.76, 95% CI: 2.74-8.62; P = 0.001) and advanced CaP (OR = 5.28, 95% CI: 3.64-8.72; P = 0.001). Furthermore, the T-Asp-b and C-Asp-b haplotypes were associated with a significantly decreased risk of CaP (OR = 0.44, 95% CI: 0.33-0.77; P = 0.004, and OR = 0.39, 95% CI: 0.26-0.61; P = 0.001, respectively). We found significant differences in genotype distribution and allelic frequencies between CaP patients and controls for the T-786C, and 4a/b eNOS polymorphisms.

Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study.

PURPOSE: We investigated the effects of the administration of ubiquinol (a reduced form of coenzyme Q(10)) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia. MATERIALS AND METHODS: A total of 228 men with unexplained infertility were randomly assigned 1:1 into 2 groups. Group 1 (114) received 200 mg ubiquinol daily by mouth for 26 weeks and group 2 (114) received a similar regimen of placebo. After completion of the 26-week treatment phase, all participants were followed for another 12-week off-drug period. Primary outcomes were improvement in sperm density, sperm motility and sperm strict morphology. RESULTS: At the end of the 26-week treatment period mean ± SD sperm density in the ubiquinol and placebo groups was 28.7 ± 4.6 × 10(6)/ml and 16.8 ± 4.4 × 10(6)/ml (p = 0.005), sperm motility was 35.8% ± 2.7% and 25.4% ± 2.1% (p = 0.008), and sperm strict morphology was 17.6% ± 4.4% and 14.8% ± 4.1% (p = 0.01) of normal sperm, respectively. During the treatment period serum follicle-stimulating hormone levels decreased significantly (p = 0.02) and serum inhibin B concentrations increased significantly (p = 0.01). During the off-drug period semen parameters gradually returned to baseline values but the differences were still significant for sperm density (p = 0.03) and sperm motility (p = 0.03). The correlation coefficients analysis revealed a positive association between the duration of treatment with ubiquinol and sperm density (r = 0.74, p = 0.017), sperm motility (r = 0.66, p = 0.024) and sperm morphology (r = 0.57, p = 0.027). CONCLUSIONS: Ubiquinol was significantly effective in men with unexplained oligoasthenoteratozoospermia for improving sperm density, sperm motility and sperm morphology.

G Protein ß3 subunit gene C825T polymorphism and its association with the presence and clinicopathological characteristics of prostate cancer.

PURPOSE: A C825T polymorphism in the GNB3 gene encodes the Gß3 subunit of heterotrimeric G proteins. Due to increased G protein activation the GNB3 825T allele, a truncated form of the G3 protein, is associated with enhanced signal transduction capacity. This splice variant is associated with various malignant diseases. We investigated the possible association of GNB3 gene polymorphism with prostate cancer and its clinicopathological characteristics. MATERIALS AND METHODS: Using polymerase chain reaction and restriction fragment length polymorphism the allele frequency of the C825T polymorphism was investigated in 172 patients with prostate cancer. Results were compared with those of 344 age matched, healthy blood donors. RESULTS: The frequency of the GNB3 825T allele in patients with prostate cancer was significantly higher than in controls (49.1% vs 42.7%, OR 3.76, p = 0.003). Patients with prostate cancer who had the TT genotype were at 2.52 times higher risk for prostate cancer than the CC genotype referent group (OR 2.22, 95% CI 1.18-4.22, p = 0.008). Accordingly a significant increased risk of advanced disease was observed in men carrying the GNB3 TT genotype compared with those homozygous for the wild-type C allele (OR 6.24, 95% CI 4.16-12.45, p = 0.001). Men lacking the C825 allele were at approximately sevenfold higher risk for high grade (Gleason score greater than 7) prostate cancer than men with the GNB3 CC genotype. CONCLUSIONS: Our study presents preliminary but intriguing data suggesting that GNB3 gene polymorphism influences susceptibility to prostate cancer.

Estrogen receptors alpha (rs2234693 and rs9340799), and beta (rs4986938 and rs1256049) genes polymorphism in prostate cancer: evidence for association with risk and histopathological tumor characteristics in Iranian men.

We evaluated the effect of estrogen receptor (ER)-α and ER-ß genes polymorphisms on development of prostate cancer (PCa) and its correlation with serum reproductive hormones and with clinicopathological characteristics in a sample of Iranian men. One hundred sixty-two men with PCa (mean age 63.7 ± 3.4 years) and 324 age-matched healthy controls (mean age 63.1 ± 3.2 years) were recruited in this study. Genotypes for ER-α and ER-ß genes polymorphisms were identified by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Serum levels of reproductive hormones were also measured. Of PCa patients, 38.3%, and 61.7% had localized and advanced tumor, and 45.7%, and 54.3%, had low grade and high-grade cancer, respectively. There was a significant difference in genotype frequency distribution of ER-α gene polymorphism (P = 0.002), and ER-ß gene polymorphism (P = 0.003) between cancer patients and controls. The ER-α Pvull C allele carriers (TC or CC) had a significantly increased risk of PCa compared with the TT homozygotes [odds ratio (OR) 3.12; 95% confidence interval (CI) 1.87-5.84, and OR = 4.73, 95% CI:2.44-7.33, respectively]. It was also found that the ER-α XbaI AG (OR = 4.36; 95% CI:2.47-6.68; P = 0.001) and ER-ß AluI AG (OR = 2.66, 95% CI:1.61-4.16; P = 0.004) genotypes were significantly associated with increased risk of PCa. The ER-ß RsaI genotype was not associated with PCa. Baseline serum free E2 levels tended to be lower in men with PCa (0.35 ± 0.04 pg/ml) compared to healthy men (0.48 ± 0.05 pg/ml). Genotypes which confer susceptibility for developing PCa, accompanied with lowest serum levels of free E2. In the Iranian population, genetic polymorphisms of the ER-α and ER-ß genes may be involved in the etiology of PCa.

Relationship of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) gene polymorphism with the susceptibility to development of prostate cancer and influence on serum levels of IGF-I, and IGFBP-3.

The bioavailability of IGF-I is controlled by the binding protein, IGF binding protein-3 (IGFBP-3). In addition, IGFBP-3 is a strong anti-proliferative protein that provokes apoptosis and inhibits cell proliferation in prostate cancer. We conducted this study to investigate the association between IGFBP-3 gene polymorphism and serum levels of IGF-I and IGFBP-3 and the incidence of prostate cancer (PCa) and benign prostatic hyperplasia (BPH). DNA isolation was performed in peripheral blood samples obtained from all participants. Required areas were amplified with polymerase chain reaction restriction fragment length polymorphism (PCR-RLFP) technique by using proper primers belonging to this gene area. We also measured serum IGF-I and IGFBP-3 levels. The IGFBP-3 -202 A/C polymorphism genotype frequencies showed a significant difference between PCa patients and controls (χ(2)=6.27, df=2.0, P=0.026), as well as between BPH patients and controls (χ(2)=11.57, df=4.0, P=0.014). The AA genotype frequency was significantly decreased in PCa and BPH patients compared to control group and the risk of PCa and BPH occurrence of this genotype was decreased accordingly (PCa; OR=0.28, 95% CI=0.17-0.44, P=0.0001; BPH: OR=0.48, 95% CI=0.29-0.77, P=0.001). Age-adjusted mean serum IGFBP-3 concentrations were highest in the individuals with the AA genotype and diminished significantly in a stepwise manner in the presence of 1 or 2 copies of the C allele (4577 ng/ml, 3929 ng/ml and 3349 ng/ml, respectively). Patients with PCa and BPH had lower serum IGF-1 (P=0.001, and P=0.01, respectively) and IGFBP-3 levels (P=0.001, and P=0.01, respectively) compared with controls. The AA genotype at IGFBP-3 gene polymorphism is associated with reduced risks of PCa and BPH. Both IGF-I and IGFBP-3 concentrations, are associated with modified risks of PCa and BPH.

The association between bladder cancer and a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) gene.

Insulin-like growth factors (IGF) regulate growth and development and enhance cellular proliferation. IGF-binding protein-3 (IGFBP-3) inhibits IGF action by competitively binding IGFs that prevents their binding to the IGF cell surface receptor. Altered expression and serum levels of IGFBP-3 are associated with a number of malignancies. Study addressing the effect of IGFBP-3 gene polymorphism on bladder cancer is lacking. The aim of this study was to examine the effect of -202 A/C polymorphism of IGFBP-3 gene on development of bladder transitional cell carcinoma (TCC) and its correlation with serum concentration of IGF-1 and IGFBP-3 and with clinicopathological characteristics. One single nucleotide polymorphism (rs2854744) was genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RLFP) technique. One hundred and sixty-two bladder cancer patients were genotyped for this SNP. The genotypes were compared with those of a random sample of 324 age-matched controls of the general population. Serum levels of IGF-I and IGFBP-3 were also determined. We found statistically significant differences in the genotypic distribution between the cases and the control subject (χ(2) = 6.43, df = 2.0, P = 0.028). Using CC genotype as a reference, the odds ratio for the subjects with AC genotype was 1.76 (95% CI: 1.27-2.84; P = 0.038). We detected a significantly decreased risk of bladder cancer associated with the AA genotype (adjusted OR = 0.48; 95% CI = 0.24-0.64; P = 0.001) compared with the CC genotype. This decreased risk was more pronounced for invasive bladder cancer. Age-adjusted mean serum IGFBP-3 levels were lowest in the individuals with the CC genotype. We found a positive correlation between age-adjusted serum IGFBP-3 levels and circulating IGF-1 concentrations (16% difference in IGFBP-3 in top vs. bottom tertiles of IGF-1, P for trend = 0.001), which was comparable across genotypes at the -202 IGFBP-3 locus (interaction term, F = 0.10, P = 0.87). Genetic polymorphism of the IGFBP-3 gene may be involved in the etiology of bladder TCC, and our results need further confirmation by larger studies.

A prospective double-blind randomized placebo-controlled study of the effect of saffron (Crocus sativus Linn.) on semen parameters and seminal plasma antioxidant capacity in infertile men with idiopathic oligoasthenoteratozoospermia.

Male factor infertility is a multifactorial disorder that affects a significant percentage of infertile couples; however, many of them remained untreated. In recent years, considerable numbers of infertile men have sought 'herbal remedies' as an effective treatment. Among 'herbal remedies', saffron is recommended for male infertility in our community. The effect of saffron was evaluated compared with placebo for the treatment of idiopathic male factor infertility. The study included 260 infertile men with idiopathic oligoasthenoteratozoospermia (OAT) who were randomized to saffron 60 mg/day (130, group 1) or a similar regimen of placebo (130, group 2) for 26 weeks. The two groups were compared for changes in semen parameters and total seminal plasma antioxidant capacity. Saffron administration did not result in beneficial effects. At the end of the study no statistically significant improvements were observed in either group in any of the studied semen parameters (sperm density, morphology and motility) (all p = 0.1). At the end of the trial, patients in group 1 had a mean motility of 25.7 ± 2.4%, which was not statistically different from the mean of 24.9 ± 2.8% in the placebo group (p = 0.1). Normal sperm morphology was 18.7 ± 4.7% and 18.4 ± 4.3%, in groups 1 and 2, respectively (p = 0.1). Patients treated with saffron and placebo had a mean sperm density of 20.5 ± 4.6% and 21.4 ± 4.6% per mL, respectively (p = 0.1). Saffron administration did not improve total seminal plasma antioxidant capacity, compared with baseline (p = 0.1) and placebo subjects (p = 0.1). Based on Pearson correlations, each semen parameter did not correlate significantly with treatment duration, including sperm density (r = 0.146, p = 0.13), percent of motile sperm (r = 0.145, p = 0.15) and percent of sperm with normal morphology (r = 0.125, p = 0.30). Saffron does not statistically significantly improve semen parameters in infertile men with idiopathic OAT. If medical professionals want to prescribe herbal remedies for male infertility, previous rigorous scientific investigations, documenting their safety and efficacy are required.

Association of the (TAAAA)n repeat and Asp327Asn polymorphisms in the sex hormone-binding globulin (SHBG) gene with idiopathic male infertility and relation to serum SHBG concentrations.

Sex hormone binding globulin (SHBG) is involved in delivering sex hormones to target tissues. We investigated the association between the (TAAAA)n repeat polymorphism, and Asp327Asn polymorphism in the SHBG gene with semen quality and idiopathic male infertility. We studied 168 men with idiopathic infertility [oligoasthenoteratozoospermia (OAT)] and equal number of age-matched normal controls. The serum levels of SHBG, reproductive and thyroid hormones, and Inhibin B were measured. Semen parameters were also assessed. The genotype assays for the SHBG polymorphism were done using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Baseline SHBG levels tended to be lower in infertile men (21.1±7.2nmol/l) compared to normal fertile men (24.7±7.9nmol/l). SHBG levels tended to be higher among the subjects with the Asn/Asn (25.84±3.6nmol/l) and S/S (24.50±5.4nmol/l) genotypes compared to subjects with the Asp/Asn (24.38±3.2nmol/l) and L/L (18.44±4.2nmol/l) genotypes of the SHBG gene. The genotype frequencies of Asp/Asp were 80.9% in cases and 71.4% in controls (P=0.001). The variant Asp/Asn genotype was associated with a more than 50% reduced risk of infertility (OR: 0.46, 95% CI: 0.25-0.80, P=0.001). Genotype analysis demonstrated six SHBG (TAAAA)n alleles with 6-11 repeats. Long SHBG (TAAAA)n alleles (>8 repeats) were at greater frequency in infertile men than fertile subjects (P=0.001), whereas short SHBG (TAAAA)n alleles (≤8 repeats) tended to be more frequent in fertile men than cases (P=0.001). Men with the 9/X TAAAA repeat genotype displayed a 2.82-fold increased risk of infertility (95% CI: 1.27-4.79, P=0.01). There were strong and significant positive correlations between plasma SHBG and sperm count (r=0.672, P=0.01), sperm motility (r=0.721, P=0.01) and sperm morphology (r=0.574, P=0.02). We concluded that the SHBG Asp237Asn and (TAAAA)n polymorphisms may influence SHBG levels and as a result, male infertility. Multicenter large scale studies are warranted to better elucidate the role of SHBG gene polymorphism in male infertility.

Association of the T-786C, G894T and 4a/4b polymorphisms of the endothelial nitric oxide synthase gene with vasculogenic erectile dysfunction in Iranian subjects.

OBJECTIVE: • To investigate the association of the T-786C, G894T and variable number of tandem repeats (VNTRs) in intron 4 (a/b) polymorphisms of the eNOS gene in Iranian subjects with vasculogenic erectile dysfunction (ED). PATIENTS AND METHODS: • A total of 322 consecutive patients with vasculogenic ED were recruited. Patients with concomitant risk factors for ED were excluded. • Patients with ED were identified based on history-taking, detailed physical examination, serum biochemistry, sex hormone measurements, application of the International Index of Erectile Function (IIEF) questionnaire, and penile duplex Doppler ultrasonography after intracavernosal injection of 20 µg prostaglandin E(1) . The control group comprised 318 age-matched healthy male volunteers. • Genotyping was performed by polymerase chain reaction-restriction fragment length polymorphism and the T-786C, G894T and VNTR intron 4 polymorphisms of the eNOS gene were determined. RESULTS: • After multivariate regression analysis, significant differences were seen in the frequencies of genotypes and alleles of the two T-786C and G894T polymorphisms when patients with ED and normal controls were compared. • In a multiple logistic regression analysis, the odds ratio (OR) of increased ED was strongly associated with the -786C allele [adjusted OR = 3.12, 95% confidence interval (CI) = 2.28-4.25; P= 0.001] and the 894T allele (adjusted OR = 3.87, 95% CI = 2.53-4.87; P= 0.001). • The data showed a higher prevalence of the T-786C CC genotype (adjusted OR = 2.72, 95% CI = 1.88-3.65; P= 0.006), and the G894T GT (adjusted OR = 1.72, 95% CI 1.24-2.83; P= 0.037) and G894T TT genotypes (adjusted OR = 3.42, 95% CI 2.42-4.26; P= 0.001) in patients with ED than in the controls. CONCLUSIONS: • The findings of the present study suggest that the eNOS T-786C and G894T polymorphisms are strong predictors of the predisposition to ED in addition to traditional risk factors, signifying a genetic influence for this multifactorial disease. • Further studies in different ethnic populations are needed to better elucidate the role of eNOS gene polymorphism in the pathogenesis of ED.