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

What's known on the subject? and What does the study add? We know that nitric oxide (NO) plays a significant role in penile tumescence. NO is produced during enzymatic conversion of L‐arginine to L‐citrulline by three distinct isoforms of NO synthase (NOS), namely, inducible (iNOS), endothelial (eNOS) and neural (nNOS). The endothelial isoform of NOS (eNOS), encoded by the NOS3 gene, is the main source of NO. We determined all three eNOS gene polymorphisms in men with vasculogenic erectile dysfunction. There was a significant difference between the group of men with vasculogenic erectile dysfunction and normal healthy men when compared by genotype distribution.

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 E₁. 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.     

The associations among eNOS G894T gene polymorphism, erectile dysfunction and related risk factors

OBJECTIVE: To investigate the possible correlations among eNOS G894T polymorphism, erectile dysfunction (ED) and related risk factors in a Taiwanese population. MATERIALS AND METHODS: In all, 151 patients with ED and 77 healthy controls were enrolled. All the men had a complete clinical history taken and laboratory data was collected. To assess erectile conditions the five-item version of the International Index of Erectile Function (IIEF-5) was used. The eNOS G894T polymorphisms were determined using the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: In all, 228 men were enrolled with a mean (sd) age of 58.6 (9.7) years. In a univariate analysis, age, serum testosterone level, and the prevalence of diabetes mellitus (DM) and hypertension were significantly different between patients with ED and the healthy controls (P < 0.01). In the multiple logistic regression analysis, DM, age and hypogonadism were three independent risk factors for ED (P = 0.018, P = 0.046 and P = 0.016, respectively). The prevalence of ED in T allele carriers (GT/TT) was significantly greater than in G allele carriers (GG; 80.0% vs 63.3%, P = 0.04). Also the eNOS 894T allele carriers had significantly lower IIEF-5 scores than the eNOS 894G allele carriers, at 13.2 (5.3) vs 15.7 (6.1) (P = 0.01) and it was associated with increment of T allele number (11.0 (5.6) vs 13.6 (5.2) vs 15.7 (6.1); P = 0.03). CONCLUSION: Our results indicate that DM, age and hypoganadism are three significant independent risk factors for ED. Also, in the Taiwanese population, the eNOS 894T allele carriers are at greater risk of ED, both in prevalence and severity, and this might be a factor of genetic susceptibility.     

Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms

Objective

To explore the correlation between post-severe acute respiratory symptom (SARS) patients with osteonecrosis, investigate the etiology of post-SARS osteonecrosis and select the sensitive molecular symbols for early diagnosis and distinguish the high-risk population.

Methods

The studied subjects were divided into two groups. Sixty-two post-SARS patients with osteonecrosis were one group, and 52 age- and sex-matched healthy people were as normal controlled group. Empty stomach blood samples from cubital veins were collected from both groups. Plasminogen activator inhibitor (PAI) by means of enzyme-linked immunosorbent assay and PAI-1 4G/5G polymorphism was detected by polymerase chain reaction and solid phase oligonucleotide assay.

Results

The blood agents of post-SARS patients changed obviously with 15.64 ± 13.85 U/ml while the control group 7.96 ± 4.27 U/ml; 4G/4G genotype for the PAI-1 polymorphism detected in post-SARS group was more than that of the control group, but had no statistical significance. The plasma PAI activity was related to homozygote 4G/4G genotype. This reveals that homozygote 4G/4G genotype may be a susceptible gene mark to Chinese osteonecrosis patients.

Conclusion

Plasminogen activator inhibitor-1 is sensitive blood symbol for screening high-risk susceptible population; 4G/4G PAI-1 genotype may be an etiological factor in osteonecrosis.     

PAI-14G/5G基因多态性与严重急性呼吸综合征后骨坏死

[目的]测定严重急性呼吸窘迫综合征(SARS)后骨坏死患者低纤溶倾向的纤溶酶原激活抑制物PAI和相关基因PAI-4G/5G基因多态性与国人SARS后骨坏死的关系,以便于非创伤性骨坏死的早期诊断和易感人群的筛选.[方法]取61例SARS后骨坏死患者抽取空腹肘静脉血.另取健康人群52名为对照,应用凝血仪、酶联免疫吸附(ELISA)方法测定PAI值,应用PCR 固相寡核苷酸连接分析(SPOLA)法测定PAI-1基因4G/5G多态性.[结果]SARS后骨坏死患者PAl异常明显PAI(15.64±1385)U/ml VS(7.96±4.27)U/ml,PAl-1基因4G/4G在骨坏死人群中增高,但统计学未见差异性,血浆PAI活性与4G/4G纯合子基因型密切相关.[结论]SARS后骨坏死患者的凝血指标异常,PAI可作为骨坏死易感因素的筛选指标.PAI-1基因4G/4G可能是国人骨坏死的遗传标记.     

Comparison of satisfaction rates and erectile function in patients treated with sildenafil,intracavernous prostaglandin E1 and penile implant surgery for erectile dysfunction in urology practice

PURPOSE: We compared erectile function status and satisfaction rates in patients who received treatment for erectile dysfunction (ED) with sildenafil, intracavernous prostaglandin E1 (ICI) and penile implant surgery (IPP). MATERIALS AND METHODS: A total of 138 consecutive patients who received treatment for ED between April 2000 and April 2001 were considered candidates for study. Mean followup was 19.54 months. Of the patients 27 were not available for followup and 26 were not on any form of treatment. Of the patients receiving treatment for ED 85 were administered the Erectile Dysfunction Inventory for Treatment Satisfaction (EDITS) questionnaire and the Erectile Function Domain (EFD) of the International Index of Erectile Function questionnaire. Three treatment groups were identified, including 31 patients on sildenafil citrate, 22 on ICI and 32 who underwent IPP. Mean total EDITS, EDITS Index and EFD scores in the 3 groups were considered for statistical evaluation. RESULTS: There was no statistical difference in the total EDITS (25.59 versus 27.06, p = 0.48), EDITS Index (58.16 versus 61.15, p = 0.49) or EFD (22.91 versus 20.26, p = 0.12) score between the groups on ICI and sildenafil citrate, respectively. Total EDITS, EDITS Index and EFD scores were significantly higher in patients who underwent IPP than those on sildenafil citrate (36.09 versus 27.06, p <0.001, 82.03 versus 61.51, p <0.001 and 27.88 versus 20.26, p <0.001, respectively). Total EDITS, EDITS Index and EFD scores were significantly higher in patients who underwent IPP than those on ICI (36.09 versus 25.59, 82.03 versus 58.16 and 27.88 versus 22.91, respectively, all p <0.001). CONCLUSIONS: At a mean followup of 19.54 months patients who underwent penile implant surgery had significantly better erectile function and treatment satisfaction than those receiving sildenafil citrate and intracavernous prostaglandin E1.     

Genetic association study of the GNB3 C825T,the ACE I/D and the eNOS G894T polymorphisms and the risk to develop erectile dysfunction in a German ED population

Erectile dysfunction (ED) is often associated with cardiovascular disorders such as hypertension, coronary heart disease, hypercholesterolaemia and diabetes mellitus. The genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms have been identified as genetic risk factors for cardiovascular disorders. The association between the genotypes in these polymorphisms and the risk to develop ED was analysed. In 455 German ED patients and 111 age‐matched healthy controls genotyping in the candidate polymorphisms was performed after DNA extraction from whole blood. Association studies between the genotype distribution in the control group in comparison with the ED‐group and age of onset of the disease as well as erectile response to intracorporal prostaglandin injection in dependence of candidate polymorphism genotype were performed using the SPSS‐Software®. Genotype distribution of the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms was similar in the ED population and the healthy control group. The age of onset of the disease as well as the erectile response to intracorporal prostaglandin injection was independent of the genotypes in the three candidate polymorphisms. In contrast to the previous studies in this analysis, the risk to develop ED is not influenced by the genotypes in the GNB3 C825T, the ACE I/D and the eNOS G894T polymorphisms.     

A case-control study on the association between chronic prostatitis/chronic pelvic pain syndrome and erectile dysfunction

Study Type – Symptom prevalence (case control) Level of Evidence 3a What's known on the subject? and What does the study add? In recent years, a number of studies have reported a high prevalence of erectile dysfunction (ED) among patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). Several studies have reported that the prevalence of ED ranges from 15.0 to 40.5% in men in China with CP/CPPS; however, the previous studies focusing on the prevalence of ED among patients with CP/CPPS all neglected to explore the magnitude of this association. Our study found an association between ED and previously diagnosed CP/CPPS. The odds of previous CP/CPPS were 3.62 times greater for cases than for controls, after adjusting for patient socio‐demographic characteristics, comorbidities, obesity, and alcohol abuse/alcohol dependence syndrome.

OBJECTIVE

• ? To examine the association between erectile dysfunction (ED) and a previous diagnosis of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) using a population‐based dataset.

PATIENTS AND METHODS

• ? The data for this case–control study was obtained from the National Health Insurance database.
• ? A total of 3194 males, who were ≥18 years of age when they first received a diagnosis of ED, were identified and 15 970 controls were randomly selected.
• ? The prevalence and risk of CP/CPPS among cases and controls were calculated by using conditional logistic regression analysis.

RESULTS

• ? In total, 667 (3.5%) of the 19 164 sampled subjects had been diagnosed with CP/CPPS before the index date; CP/CPPS was found in 276 (8.6%) cases and in 391 (2.5%) controls (P < 0.001).
• ? Regression analysis indicated that cases were more likely to have had previous CP/CPPS (odd ratio 3.62, 95% confidence interval 3.07–4.26) after adjusting for patient monthly income, geographical location and urbanization level, as well as hypertension, diabetes, coronary heart disease, renal disease, obesity and alcohol abuse/alcohol dependence syndrome status, when compared with controls.

CONCLUSIONS

• ? We conclude that there was an association between ED and having been previously diagnosed with CP/CPPS.
• ? Urologists should be alert to the association between CP/CPPS and ED, and assess the erectile function of patients suffering from CP/CPPS.

     

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.     

The association between therapeutic outcomes and VEGF G-1154A and C-936T gene polymorphisms in patients with glomerulonephritis

Background: In this present study, we aimed to investigate the association between therapeutic outcomes and vascular endothelial growth factor (VEGF) G-1154A and C-936T gene polymorphisms in patients with glomerulonephritis. Methods: Thirty-eight patients with glomerulonephritis diagnosed by renal biopsy were included to the study. All patients had proteinuria at least 1 gram (g)/day in urine analysis. At the end of a yearly therapy, patients with proteinuria less than 0.5?g/day were accepted as in complete remission and they were termed as group 1. The patients with proteinuria over 0.5?g/day were accepted as in no remission and they were termed as group 2. Results: The mean age of patients in group 1 and group 2 was 35.88?±?13.80 years and 37.30?±?13.89 years, respectively. There were nine (50%) male and nine (50%) female patients in group 1. In group 2, seven (35%) male and 13 (65%) female patients were present. Although VEGF G-1154A (GG) gene polymorphism was found in 55% of group 2 patients, and 22.2% of group 1 patients, but the differences did not reach statistical significance. There were no statistical differences between groups in terms of other gene polymorphisms. Namely, we obtained no statistical differences between therapeutic outcomes and gene polymorphisms. Conclusions: There is a significant difference between groups in terms of VEGF G-1154A (GG) gene polymorphism, but the minority of the patient population has led to not to reach statistical significance. So, this gene polymorphism has to be investigated in larger studies.     

PRM1基因C321A、G197T单核苷酸多态性对体外受精结局的影响

目的 探讨鱼精蛋白1的C321A、G197T基因多态性与体外受精结局的关系。方法 选取我院生殖中心进行常规IVF的182例(182个周期),根据受精率分为3组:A组受精率30%,43个周期;B组受精率在30%~65%之间,24个周期;C组受精率65%,115个周期。提取授精后剩余精子的基因组DNA,采用聚合酶链限制性片段长度多态性(PCRRFLP)方法检测PRM1基因C321A和G197T基因型频率和分布,比较3组间基因型的分布差异及所有研究对象不同基因型间受精率的差异。结果 3组间比较,PRM1基因C321A多态性位点的各基因型频率无显著性差异(P0.05),C321A多态性位点与IVF受精率无相关性(P0.05)。在A组中,PRM1基因G197T多态性位点GG、GT、TT基因型分布频率分别为9.3%(4)、25.6%(11)、65.1%(28);B组分别为8.3%(2)、25.0%(6)、66.7%(16);C组分别为38.3%(44)、26.1%(30)、35.6%(41)。A组和B组的TT基因型频率显著高于C组(65.1%vs.35.6%,66.7%vs.35.6%),差异均有统计学意义(P0.05),TT基因型增加了IVF受精失败的风险。结论 PRM1基因C321A多态性与IVF受精率不相关;PRM1基因G197T多态性改变与IVF受精率相关。     

胃癌易感性与细胞毒性T淋巴细胞相关抗原-4基因+49A/G多态性的关系

目的 探讨细胞毒性T淋巴细胞相关抗原-4(CTLA-4)基因外显子1区+49A/G位点多态性在中国人群中的分布及其与胃癌易感性的关系.方法 应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法检测205例胃癌患者和262例正常对照者CTLA-4基因+49A/G多态位点基因型频率,进行多态性与胃癌易感性的关系分析并进行分层分析.结果 CTLA-4基因外显子1区+49位点A/G、G/G基因型在胃癌组患者中的分布频率明显高于对照组(P＜0.01,OR=2.146;P＜0.01,OR=3.215);分层分析示:男性患者、年龄在40～55岁之间、不吸烟、不饮酒患者组等组别的胃痛患者携带G/G基因型的频率较正常对照组显著增加.结论 CTLA-4基因外显子1区+49A/G多态性与胃癌易感性有明显相关,携带A/G、G/G基因型的个体胃癌发病风险增加,分层因素也影响这一结果.     

Association between the insertion/deletion polymorphism of the angiotensin-converting enzyme gene and erectile dysfunction in patients with metabolic syndrome

This study was designed to investigate whether angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism is associated with erectile dysfunction (ED) in Russian men with metabolic syndrome (MS). A total of 331 men with MS were studied. All patients underwent complex evaluation including the International Index of Erectile Function (IIEF) questionnaire. The ACE I/D polymorphism was determined by polymerase chain reaction. Overall, 182 men (55.0%) had ED according to the IIEF erectile function domain score. In the ED group, the prevalence of DD genotype was found to be significantly higher compared to the non-ED group (P<0.001). In both groups, patients with DD genotype were significantly younger than patients with other genotypes (P<0.001). In addition, in the ED group, the disease affected patients with DD genotype at a significantly younger age (P<0.001). Obtained results give evidence to support the finding that the D allele is a risk factor for the micro- and macrovascular diseases.     

Association between the RAGE gene -374T/A, -429T/C polymorphisms and diabetic nephropathy: a meta-analysis

Abstract

Aim: The investigations into the association between the receptor for advanced glycation end products (RAGE) gene -374T/A, -429T/C polymorphisms and diabetic nephropathy (DN) in several case–control studies have rendered conflicting results. To shed light on these inconclusive findings, a meta-analysis of all the eligible studies relating these two polymorphisms to the risk of DN was conducted. Methods: The databases were searched for relevant articles up to July 2014. A pooled estimate of the genetic association, the heterogeneity between studies, and the publication bias were investigated. Results: Eight studies with 1725 cases and 1857 controls were enrolled in -374T/A polymorphism analysis. The main analysis indicated no association for the allele contrast, the recessive model and the dominant model. Subgroup analyses in Caucasians and in type 2 diabetes also showed no association between -374T/A polymorphism and DN. Five studies with 1019 cases and 792 controls were enrolled in -429T/C polymorphism analysis. The main analysis revealed heterogeneity and no association for the allele contrast and the dominant model. However, the recessive model for -429C allele diminished the heterogeneity and showed a marginal association overall [fixed-effects OR?=?2.83 (1.33–6.00) and random effects OR?=?2.50 (1.00–6.24), respectively]. Conclusions: Our meta-analysis indicated that the RAGE gene -429CC genotype might be a risk factor for DN in patients with type 2 diabetes.     

eNOS gene T786C,G894T and 4a4b polymorphisms and male infertility susceptibility: a meta‐analysis

The association between polymorphism of eNOS and male infertility in several studies was controversial. To explore a more precise estimation of the association, a meta‐analysis of eight case–control studies, including 1,968 cases and 1,539 controls, were selected. The meta‐analysis was conducted by calculating the pooled odds ratio (OR) with a 95% confidence interval (95% CI). Overall, the association between T786C and risk of male infertility was obvious (TC vs. TT: OR, 1.20; 95% CI, 1.01–1.42; CC vs. TT: OR, 3.37; 95% CI, 1.65–6.87; TC/CC vs. TT: OR, 1.47; 95% CI, 1.25–1.73; CC vs. TT/TC: OR, 3.18; 95% CI, 1.54–6.56; TC vs. TT: OR, 1.65; 95% CI, 1.27–2.03). However, no overall association was observed between the other two polymorphisms of eNOS (G894T and 4a4b) and male infertility. Stratified analysis showed that significantly strong association between T786C polymorphism and semen quality was present in all three types of male infertility (azoospermia, oligozoospermia and asthenozoospermia). In the subgroup analysis based on ethnicity, both T786C and 4a4b could influence the risk of male infertility in Asian and Caucasian. Further studies of polymorphisms of eNOS with their biological functions are needed to understand the role in the development of male infertility.     

A baseline-controlled,open-label,flexible dose-escalation study to assess the safety and efficacy of sildenafil citrate (Viagra) in patients with erectile dysfunction

Although sildenafil citrate (Viagra) has demonstrated effectiveness in the treatment of erectile dysfunction (ED), the dosing regimens often used in clinical trials may not always match those employed in clinical practice. This study was undertaken to further assess the efficacy and safety of sildenafil taken as required in male outpatients 18 years of age and older with ED (n=71). It was conducted as a placebo-baseline-controlled, open-label, flexible dose-escalation study, with sildenafil (25,50, or 100 mg) administered for 8 weeks following a 4-week placebo run-in. Efficacy variables included questions 3 and 4 of the International Index of Erectile Function (IIEF), other IIEF domains, patient event logs, and quality-of-life (QOL) assessments. Treatment with sildenafil resulted in improvements from baseline in all IIEF domains analyzed (all P<0.0001), as well as overall QOL and amelioration of specific sexual and social relationships (all P&<0.0001). Sildenafil was well tolerated. One participant discontinued treatment because of adverse events. Results suggest that flexible dosing with oral sildenafil is safe and has beneficial effects on all indices of erectile function and QOL.     

No association of factor V Leiden, prothrombin G20210A, and MTHFR C677T gene polymorphisms with kidney allograft survival: a multicenter study

BACKGROUND: It has been proposed that inherited risk factors of venous thromboembolism, such as factor V G1691A (FV-Leiden), prothrombin G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T, might be associated with poorer survival rates of transplanted kidneys. On the basis of this hypothesis, we performed a multicenter study, involving recipients of primary and repeat kidney transplants, to investigate the potential effect of these three single nucleotide polymorphisms (SNP) on graft survival. METHODS: The study consisted of 676 first and 651 retransplant patients. Using the polymerase chain reaction-sequence specific primers method, we typed all patients for the three SNP and analyzed graft survival. RESULTS: We could not find a statistically significant association between graft survival and factor V Leiden or MTHFR C677T genotypes. A better 3-yr graft survival was found for first transplant recipients with the genotype prothrombin 20210 G/G as compared to those with the G/A genotype (P=0.031). However, Bonferroni correction for the three SNPs investigated in this series rendered the P value insignificant (P(corrected)=0.093). CONCLUSION: We did not find a statistically significant association of SNP factor V Leiden G1691A and MTHFR C677T with renal graft survival. Prothrombin G20210A resulted in a significant association that was not sustained after Bonferroni correction. This SNP might be an interesting candidate for future studies.     

PAI-1 4G/5G and ACE I/D gene polymorphisms and the occurrence of myocardial infarction in patients on intermittent dialysis.

BACKGROUND: Myocardial infarction (MI) is a leading cause of death, particularly in high-risk settings such as uraemia, in which it is not yet known to what extent genetic factors contribute to the overall risk of MI. We have prospectively evaluated the effect of plasminogen activator inhibitor-1 (PAI-1) 4G/5G and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms on the occurrence of MI in uraemics. METHODS: All patients undergoing intermittent dialysis in an Italian district were enrolled as subjects. From the same area, 1307 individuals served as controls. Genomic DNA was obtained and ACE I/D and PAI-1 4G/5G gene polymorphisms were determined. After a baseline evaluation, patients were followed for 28.8+/-9.8 months. MIs and other causes of death were recorded. RESULTS: A total of 461 patients (417 on haemodialysis and 44 on peritoneal dialysis) were investigated. At entry, their mean age was 58.2+/-16.2 years and dialytic age was 82+/-69 months. Genotype frequencies were not different between controls and uraemics and, in the latter group, between patients with or without cardiovascular diseases at baseline evaluation. During the follow-up, 22 fatal and 16 non-fatal MIs were recorded (mean incidence 1.99 and 1.45%/year, respectively). The adjusted risk of fatal and total MI was related to the presence at entry of a history of MI [hazard ratios (HR) 4.3; 95% confidence interval (CI) 1.5-12.0 and HR 6.8; 95% CI: 3.3-14.0, respectively] and to the PAI-1 4/4 genotype (HR 2.8; 95% CI 1.2-6.9 and HR 2.1; 95% CI 1.1-4.2, respectively). CONCLUSIONS: In end-stage renal disease, PAI-1 4G/5G gene polymorphism may have a significant role in the occurrence of fatal and non-fatal MI.     

Meta‐analysis of the association of oestrogen receptor‐beta gene RsaI (G/A) and AluI (A/G) polymorphisms with male infertility

A more precise assessment of association of oestrogen receptor‐beta genes RsaI(G/A) and AluI(A/G) polymorphisms with male infertility from current contradictory results is the aim of this meta‐analysis including five RsaI and six AluI studies respectively. No association was observed between infertility and RsaI or AluI. In the stratified analysis by ethnicity, increased risk was found among Caucasians with GA versus GG (OR = 2.263, 95% CI = 1.073–4.776, I² = 57.1%) and dominant model (OR = 2.117, 95% CI = 1.018–4.403, I² = 49.0%) of RsaI. It was not observed for AluI. In the stratified analysis by infertility subtypes, a reduced risk in GA of AluI was observed among azoospermia or severe oligospermia (GA versus AA: OR = 0.686, 95% CI = 0.498–0.945, I² = 21.2%; recessive model: OR = 1.403, 95% CI = 1.056–1.864, I² = 31.7%), and reduced risk was in recessive model (OR = 0.650, 95% CI = 0.446–0.948, I² = 0.0%) of subtypes, except for azoospermia or severe oligospermia. However, this finding was not observed in RsaI. The meta‐analysis showed GA and GG of AluI are possibly resistant factors for spermatogenesis dysfunction and deteriorated sperm quality.