C242T Polymorphism Research Articles

Association of MMP-9 C-1562T polymorphism with risk of Henoch-Schönlein purpura nephritis in children of southeast China

Henoch-Schonlein purpura nephritis (HSPN) is the most prevalent vasculitis in childhood worldwide. Although the etiology of HSPN is not yet fully elucidated, it is believed to be closely related with infections and genetic predispositions. In this study, a cohort of children from southeast China, including 108 healthy controls and 184 patients were involved in. We scanned the promoter region and the whole gene for genetic variations. A C/T transition located in the promoter region of MMP-9 gene, C-1562T was identified. Subjects were genotyped by using SNaPshot sequencing and the frequencies of CC, CT and TT genotypes were 43, 33 and 24% in patients and 53, 37 and 10% in healthy controls. Allele distribution was found to be in Hardy–Weinberg equilibrium (P = 0.17). Association analysis revealed that the polymorphism was significantly related with HSPN risk (P < 0.05) and T allele was shown to be a risk factor (P = 0.003, odds ratio (OR) 1.63, 95% confidence interval (CI) 1.13–2.34). Additionally, we measured the serum MMP-9 concentration and quantified the mRNA expression. Results showed that an elevated protein level was observed in patients compared with controls in both ELISA (P = 0.0029, 136.5 μg/L vs. 103.9 μg/L) and Western blot assays. Furthermore, we also detected 1.93-fold increase in the mRNA transcription in patients carrying homozygous TT genotype, indicating enhanced promoter activity caused by the polymorphism. Based on the incidence risk, a cut-off value of serum MMP-9 served as HSPN diagnosis was suggested at 155 μg/L. Conclusively, our findings suggested that MMP-9 polymorphism was significantly associated with HSPN susceptibility, and C-1562T T allele contributed to HSPN development.

Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease

Endothelial Nitric Oxide Synthase (eNOS) is crucial for vascular homeostasis. Polymorphisms T786C and G894T affect eNOS regulation and have been related to various diseases. Sickle Cell Disease (SCD), a clinically diverse chronic hemolytic anemia, implies impaired nitric oxide bioavailability. Our aim was to determine eNOS genotype for T786C and G894T polymorphisms in Greek patients with SCD and to elucidate its consequences and effects if any on clinical phenotype. Seventy nine steady state cases, mostly compound heterozygous for Sickle Cell anemia/beta thalassemia and 48 controls were measured. Peripheral blood DNA was extracted and genotyped with PCR-RFLPs and Sanger sequencing. Total RNA was extracted from 18 patients and 9 controls and eNOS mRNA levels were determined by real-time PCR. Genotypes, allele distribution and eNOS mRNA levels did not differ between patients and controls, or among patients with different beta globin gene mutations. The 786CC genotype was more common in S/S and β0/S patients with retinopathy. Moreover, 894TT S/S and β0/S patients tended to have a higher hematocrit than 894GG and GT ones. However, the T786C eNOS genotype does not seem to affect peripheral blood cell-derived eNOS mRNA levels, at least in steady state conditions. This work is the first one describing the effects of eNOS polymorphisms on different forms of SCD, the first enrolling SCD patients of Caucasian origin and the first determining eNOS mRNA levels in peripheral blood from steady-state SCD patients.

Enhanced circulating transforming growth factor beta 1 is causally associated with an increased risk of hepatocellular carcinoma: a mendelian randomization meta-analysis.

The aim of this study was to test the causal association between circulating transforming growth factor beta 1 (protein: TGF-β1 and coding gene: TGFB1) and hepatocellular carcinoma by choosing TGFB1 gene C-509T polymorphism as an instrument in a Mendelian randomization (MR) meta-analysis. Ten English articles were identified for analysis. Two authors independently assessed each article and abstracted relevant data. Odds ratio (OR) and weighted mean difference (WMD) with 95% confidence interval (CI) were synthesized under a random-effects model. Overall, the association of C-509T polymorphism with hepatocellular carcinoma was negative, but its association with circulating TGF-β1 was statistically significant, with a higher concentration observed in carriers of the -509TT genotype (WMD, 95% CI, P: 1.72, 0.67–2.78, 0.001) and -509TT/-509TC genotypes (WMD, 95% CI, P: 0.98, 0.43–1.53, < 0.001). In subgroup analysis, C-509T polymorphism was significantly associated with hepatocellular carcinoma in population-based studies under homozygous-genotype (OR, 95% CI, P: 1.74, 1.08–2.80, 0.023) and dominant (OR, 95% CI, P: 1.48, 1.01–2.17, 0.047) models. Further MR analysis indicated that per unit increase in circulating TGF-β1 was significantly associated with a 38% (95% CI: 1.03–4.65) and 49% (95% CI: 1.01–6.06) increased risk of hepatocellular carcinoma under homozygous-genotype and dominant models, respectively. Conclusively, based on a MR meta-analysis, our findings suggest that enhanced circulating TGF-β1 is causally associated with an increased risk of hepatocellular carcinoma.

No association between TGF-β1 polymorphisms and risk of nasopharyngeal carcinoma in a large North African case-control study.

BackgroundGenetic susceptibility plays a key role in the development of nasopharyngeal carcinoma (NPC) and in fact the disease presents with an unusually high incidence in certain regions of the world like North Africa. We investigated the association between polymorphism of the Transforming growth factor-β1 (TGF-β1) and risk of NPC in North Africa. TGF-β1 is a multifunctional cytokine that acts as both a tumor suppressor and a stimulator of cancer development; it has been shown to influence risk of numerous other carcinomas including lung, breast and prostate cancer.MethodsTGF-β1 polymorphisms C-509T and T869C were studied in a large North African sample of 384 NPC cases and 361 controls, matched for age, sex and urban or rural residence in childhood. Genotypes were determined using polymerase chain reaction–restriction fragment length polymorphism.ResultsNo association was observed between individual single nucleotide polymorphisms or their haplotypes and NPC susceptibility (for TGF-β1 C-509T: OR = 0.74; 95 % CI 0.46 − 1.18; for TGF-β1 T869C: OR = 0.86; 95 % CI 0.56 − 1.31), even when the samples were stratified by age, gender and TNM stage.ConclusionContrary to what has been observed in Asian samples, in our North African sample, the TGF-β1 C-509T and T869C polymorphisms did not substantially influence NPC susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1186/s12881-016-0337-8) contains supplementary material, which is available to authorized users.

An updated meta-analysis of transforming growth factor-β1 gene: Three well-characterized polymorphisms with asthma

The association between TGF-β1 polymorphisms and asthma risk has been widely reported, but results were controversial. We performed this meta-analysis based on the Preferred Reporting Items for Systematic Reviews and meta-analyses statement (PRISMA). Electronic database of Pub Med, Web of Science, CBM, and CNKI were searched for eligible articles published up to September, 2013. The effect summary odds ratio (OR) and 95% confidence intervals were obtained. Finally, a total of 20 articles were identified, 17 studies with 3694 cases and 5613 controls for C-509T polymorphism, 7 studies with 1109 cases and 1098 controls for T869C polymorphism and 5 studies with 849 cases and 829 controls for G915C polymorphism. For C-509T, significant associations with asthma were found in Asians (TT+TC vs. CC: P=0.004, OR=1.43, 95%CI=1.12–1.81, Pheterogeneity=0.001) and in Caucasians (P=0.05, OR=1.16, 95%CI=1.00–1.34, Pheterogeneity=0.36). With respect to T869C, a small significant association was observed in overall analysis of allele contrasts(C vs. T: OR=1.14, 95%CI: 1.01–1.29, P=0.03) and homozygote comparison (CC vs. TT: OR=1.29, 95%CI: 1.00–1.65, P=0.05), but no significant risks were found among Caucasian population and Asian population. For G915C polymorphism, no significant association with asthma risk was demonstrated in overall analysis and subgroup analyses according to ethnicity for all genetic models. This meta-analysis suggested that TGF-β1 C-509T and T869C polymorphisms may be risk factors for asthma.

GW27-e0196 Association of the T786C Polymorphism of the endothelial nitric oxide synthase Gene with Essential Hypertension: a Meta-Analysis

GW27-e0196 Association of the T786C Polymorphism of the endothelial nitric oxide synthase Gene with Essential Hypertension: a Meta-Analysis

Ассоциация полиморфизмов I/D и T-786С генов ACE и NOS3 с особенностями течения ишемической болезни сердца на фоне сахарного диабета 2-го типа

to study relationship of ACE insertion-deletion (I/D) polymorphism and NOS3 T-786C polymorphism with characteristics of the course of ischemic heart disease (IHD) at the background of diabetes mellitus. Were examined 114 patients with IHD, 29.8% of patients had type 2 diabetes mellitus. ACE and NOS3 polymorphisms were determined by allele-specific polymerase chain reaction with primers by "Lytech". Patients with combined pathology belonged to older age group, had increased frequency of obesity and predominance of functional class II chronic heart failure. In this group we detected association of D allele of the ACE gene with higher frequency of dyslipidemia and obesity. Among patients with IHD without diabetes we observed associations of ACE I/D and NOS3 T-786C polymorphisms (close and moderate, respectively) with severity of effort angina. We also found that frequency of dyslipidemia among carriers of II and TT genotypes was lower than among carriers of other genotypes. Presence of type 2 diabetes as background pathology leads to a change of character of association of ACE I/D and NOS3 T-786C polymorphisms with clinical characteristics of patients with IHD.

Association Between HIF-1 Alpha Gene Polymorphisms and Response in Patients Undergoing Neoadjuvant Chemotherapy for Locally Advanced Cervical Cancer

BackgroundThe aim of the study was to assess whether HIF-1α polymorphisms have an effect on the response to chemotherapy of locally advanced cervical cancer (LACC) patients treated with platinum-based neoadjuvant chemotherapy (NACT) and radical surgery.Material/MethodsWe conducted a retrospective study in 162 LACC patients. Hypoxia-inducible factor 1α C1772T and G1790A genetic polymorphisms were ascertained using direct sequencing methods.ResultsThe C1772T polymorphism was significantly related to response to chemotherapy (P=0.002), and there was an increased chance of treatment response in patients with the C/C genotype (OR=4.7; 95% CI: 1.67–13.49; P=0.004). The C1772T polymorphism was also associated with poor tumor grade (adjusted OR, 2.98; 95% CI: 1.08–8.13; P=0.037). However, The G1790A polymorphism was not associated with response (P>0.05).ConclusionsThe C1772T polymorphism was significantly related to response to chemotherapy and poor tumor grade. Our results may help to better manage individual patients and to improve clinical decision making regarding use of NACT.

Investigation of hypoxia-inducible factor-1alpha (HIF-1α) gene polymorphisms in individuals with high levels of hemoglobin / Hemoglobin seviyesi yüksek bireylerde hipoksi ile indüklenen faktör-1 alfa (HIF-1α) gen polimorfizminin araştırılması

Abstract Objective: A classic physiologic response to systemic hypoxia is the increase in red blood cell production. Hypoxia-inducible factors (HIFs) orchestrate oxygen-sensing machinery and hypoxic cell metabolism. Recent works suggest that mutation of the HIF oxygen-sensing pathway plays a key role in the pathogenesis of the erythrocytosis. In the present study, the probable role of the polymorphic HIF-1α variants, C1772T (P582S) (rs11549465) and G1790A (A588T) (rs115494657), which are known to enhance transcriptional activity, were evaluated in the etiology of the polycythemia. Methods: A total of 284 subjects 97 with normal levels of hemoglobin (Hgb) 157 with high levels of Hgb, and 30 with polycythemia vera (PV)) were recruited for this study. Genomic DNA was extracted from peripheral blood lymphocytes of all subjects. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was performed for HIF-1α C1772T and G1790A single nucletide polymorphisms (SNP). A complete blood count was performed for all subjects. Results: There was a significant decrease in the frequency of the HIF-1α C1772T allele T in subjects with PV compared with those in the normal level Hgb group (OR 0.51; 95% CI 0.75−0.95; p=0.03). High level Hgb subjects had a significantly higher frequency of the HIF-1α G1790A allele A (OR 10.79; 95% CI 0.62-; 187.96; p=0.027) than the subjects in the normal level Hgb group. A significant difference was observed in genotype distribution of GG and combined GA+AA genotypes of HIF-1α G1790A in PV and normal Hgb level subjects (OR 17.11; 95% CI 0.80−366,61; p&gt;0.05). Conclusion: Our results suggest that the HIF-1α C1772T and G1790A polymorphisms may be associated with PV in the study population.

Matrix metalloproteinase-2, -9, and tissue inhibitor of MMP-2 gene polymorphisms in Taiwanese periodontitis patients

Background/purposeMatrix metalloproteinases (MMPs) and tissue inhibitor of MMPs (TIMPs) have been shown to play an important role in the pathogenesis of tissue destruction in periodontitis. The associations between single nucleotide polymorphisms (SNPs) in the promoter regions of MMP-2, MMP-9, and TIMP-2 genes and the risk of aggressive periodontitis (AgP) and chronic periodontitis (CP) were investigated in a Taiwanese population. Materials and methodsMMP-2 C-1306T, C-735T, T-790G, and MMP-9 C-1562T and TIMP-2 G-418C SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis in 69 patients and 129 patients with AgP and CP, respectively, and 117 periodontal healthy individuals who served as healthy controls (HC). Chi-square test and logistic regression analysis were used to investigate the possible association of genotypes with periodontitis. ResultsNo significant differences in the distributions of the C-1306T and C-735T variants between periodontitis and HC were detected. Patients with genotype of MMP-2 -790 TT or T allele of MMP-2-790T/G as compared to genotypes of GT + GG genotypes or G allele, were less susceptible to CP [odds ratio (OR) = 0.50, 95% confidence interval (CI) = 0.25–1.00 and OR = 0.52, 95% CI = 0.28–0.96, respectively]. The frequencies of TIMP-2 G-418C gene polymorphisms in nonsmokers were statistically significantly different among AgP, CP, and HC groups (P = 0.024). The nonalcohol drinking participants with C allele of MMP-9 C-1562T as compared to T allele, were less susceptible to AgP (adjusted OR = 0.4; 95% CI, 0.18–0.90). ConclusionIt is suggested that MMP-2 T-790G, MMP-9 C-1562T, and TIMP-2 G-418C gene polymorphisms might be associated with periodontitis in the Taiwanese Han population.

The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial growth factor serum levels in type 2 diabetes patients

The impact of T786C and G894T polymorphisms of eNOS on vascular endothelial growth factor serum levels in type 2 diabetes patients

TGF-β1 rs1982073 polymorphism contributes to radiation pneumonitis in lung cancer patients: a meta-analysis.

Transforming growth factor beta 1(TGF‐β1) polymorphism was associated with radiation pneumonitis (RP) susceptibility, but their results have been inconsistent. The PubMed and CNKI were searched for case‐control studies published up to Januray 01, 2016 was Data were extracted and pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated. In this meta‐analysis, we assessed eight publications involving 368 radiation pneumonitis cases and 855 controls of the association between TGF‐β1 T869C (rs1982073) and G915C (rs1800471) polymorphism and RP susceptibility. Our analysis suggested that TGF‐β1 T869C rs1982073 polymorphism was associated with lower RP risk for CT combined CC versus TT model (OR = 0.58, 95% CI = 0.43–0.77). However, for the G915C rs1800471 polymorphism, no association was found between the polymorphism and the susceptibility to RP in GC combined CC versus GG model (OR = 0.82, 95% CI = 0.50–1.35). These results from the meta‐analysis suggest that T869C rs1982073 polymorphism of TGF‐β1 may be associated with RP risk, and there may be no association between G915C polymorphism and RP risk.

Associations between eNOS polymorphisms and susceptibility to systemic lupus erythematosus and rheumatoid arthritis: ameta-analysis.

The aim of this study was to determine whether endothelial nitric oxide synthase (eNOS) polymorphisms are associated with susceptibility to systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Ameta-analysis was conducted on associations between the 4b/a, T786C, and G894T polymorphisms of eNOS and SLE or RA using the following methods: (1)allele contrast, (2)recessive model, (3)dominant model, and (4)homozygous contrast. Nineteen studies were included in this meta-analysis, comprising eleven studies on SLE (1561 patients and 1565 controls) and eight on RA (1624 patients and 2118 controls). Meta-analysis showed asignificant association between SLE and the 4b/a polymorphism using the recessive model and the homozygous contrast (odds ratio [OR]= 1.836, 95 % confidence interval [CI]= 1.171-2.878, p= 0.008; OR= 2.055, 95 % CI= 1.302-3.243, p= 0.002). Ethnicity-specific meta-analysis showed asignificant association between the aa vs. bb of the 4b/a polymorphism and SLE in European populations (OR= 2.096, 95 % CI= 1.288-4.0, p= 0.027), but not in Arab populations. Stratification by presence of lupus nephritis (LN) indicated asignificant association between the aallele and the aa+ ab genotype of the 4b/a polymorphism and LN in SLE patients (OR= 2.125, 95 % CI= 1.289-3.054, p= 0.003; OR= 2.655, 95 % CI= 1.509-4.671, p= 0.001). Meta-analysis indicated no association between SLE and the T786C and G894T polymorphisms. No association was found between the eNOS 4b/a, T786C, and G894T polymorphisms and RA CONCLUSIONS: This meta-analysis of published studies shows that the eNOS 4b/a polymorphism may be associated with the development of SLE, but the 4b/a, T786C, and G894T polymorphisms may be not associated with RA susceptibility.

Transforming Growth Factor-β1 T869C Gene Polymorphism Is Associated with Acquired Sick Sinus Syndrome via Linking a Higher Serum Protein Level

BackgroundFamilial sick sinus syndrome is associated with gene mutations and dysfunction of ion channels. In contrast, degenerative fibrosis of the sinus node tissue plays an important role in the pathogenesis of acquired sick sinus syndrome. There is a close relationship between transforming growth factor-β1 mediated cardiac fibrosis and acquired arrhythmia. It is of interest to examine whether transforming growth factor-β1 is involved in the pathogenesis of acquired sick sinus syndrome.MethodsOverall, 110 patients with acquired SSS and 137 age/gender-matched controls were screened for transforming growth factor-β1 and cardiac sodium channel gene polymorphisms using gene sequencing or restriction fragment length polymorphism methods. An enzyme-linked immunosorbent assay was used to determine the serum level of transforming growth factor-β1.ResultsTwo transforming growth factor-β1 gene polymorphisms (C-509T and T+869C) and one cardiac sodium channel gene polymorphism (H588R) have been identified. The C-dominant CC/CT genotype frequency of T869C was significantly higher in acquired sick sinus syndrome patients than in controls (OR 2.09, 95% CI 1.16–3.75, P = 0.01). Consistently, the level of serum transforming growth factor-β1 was also significantly greater in acquired sick sinus syndrome group than in controls (5.3±3.4 ng/ml vs. 3.7±2.4 ng/ml, P = 0.01). In addition, the CC/CT genotypes showed a higher transforming growth factor-β1 serum level than the TT genotype (4.25 ± 2.50 ng/ml vs. 2.71± 1.76 ng/ml, P = 0.028) in controls.ConclusionTransforming growth factor-β1 T869C polymorphism, correlated with high serum transforming growth factor-β1 levels, is associated with susceptibility to acquired sick sinus syndrome.

ENOS gene T786C, G894T and 4a4b polymorphisms and male infertility susceptibility: a meta-analysis.

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.

Relationship between endothelial nitric oxide synthase (eNOS) and natural history of intracranial aneurysms: meta-analysis.

The aneurysmal subarachnoid hemorrhage is a major public health problem described as a sudden drastic event with no warning symptoms and high morbidity and mortality rates. The role of the endothelial isoform of nitric oxide synthase gene polymorphism in intracranial aneurysms (IAs) is still a matter of controversy with divergent findings among European, American, and Asian populations. Our study purposed to test the association between intracranial aneurysms formation and nitric oxide gene polymorphisms through a systematic review and meta-analysis. Systematic search on Medline, Lilacs, and EMBASE was performed. The primary search resulted in 139 papers, out of which 9 met our inclusion criteria after a full text analysis. The dominant T786C model found a significant association with IA (OR 1.22, 95% CI 1.04-1.44, p = 0.01), so did studies of the recessive T786C model (OR 0.37, 95% CI 0.30-0.45, p < 0.0001) but with opposite effect. Our findings support the presence of the T786C polymorphism as a predictor for the development of intracranial aneurysm in the cerebral vascular system. More studies are necessary in order to elucidate the pathways of the endothelial nitric oxide synthase (eNOS) in cerebrovascular diseases and in defining how different allelic combinations of the eNOS gene single-nucleotide polymorphism (SNP) could favor this pathological process.

Association of eNOS polymorphisms with susceptibility to osteonecrosis of the femur head : Ameta-analysis.

The aim of the present study was to determine whether polymorphisms of the endothelial nitric oxide synthase (eNOS) gene are associated with susceptibility to osteonecrosis of the femoral head (ONFH). We conducted ameta-analysis to assess the association between the 4b/a, G894T, and T786C polymorphisms of eNOS and the susceptibility to ONFH. Atotal of five studies, which included 566cases and 833controls, were included in the meta-analysis. Meta-analysis revealed asignificant association between allele aof the 4b/a polymorphism and ONFH in all study subjects (odds ratio, OR 3.237; 95 % confidence interval, CI 2.036-5.148; P= 6.9× 10-7); stratification by ethnicity indicated an association between this allele and ONFH in Caucasians and Asians (OR 2.985; 95 % CI 1.592-5.597; P= 0.001 and OR 3.567; 95 % CI 1.793-7.095; P= 2.9× 10-4, respectively). Meta-analysis stratified by ONFH type showed asignificant association between allele aof the 4b/a polymorphism and idiopathic and secondary ONFH (OR 3.411; 95 % CI 2.049-5.679; P= 2.4× 10-6 and OR 3.163; 95 % CI 1.781-5.619, P= 8.6× 10-5, respectively). However, the meta-analysis did not show any allelic association between the G894T and T786C polymorphisms and ONFH (OR 1.718; 95 % CI 0.796-3.707; P= 0.168 and OR 1.027; 95 % CI 0.191-5.517; P= 0.976, respectively). Our meta-analysis of published studies shows that the 4b/a polymorphism is associated with the development of idiopathic and secondary ONFH in Caucasians and Asians.

Age and gender differences in the influences of eNOS T-786C polymorphism on arteriosclerotic parameters in general population in Japan.

The influence of T-786C polymorphism in the promoter region of endothelial nitric oxide synthase (eNOS) on arteriosclerotic parameters by age and gender were examined. Brachial-ankle pulse wave velocity (baPWV), heart-rate adjusted augmentation index (AIx@75), pulse pressure (PP) and albumin-creatinine ratio (ACR) were assessed as arteriosclerotic parameters in addition to non-high-density lipoprotein cholesterol (non-HDL-C) to HDL-C (non-HDL-C/HDL-C) ratio in 1499 participants. T-786C polymorphism (rs2070744) was screened using a TaqMan allelic discrimination assay. Analyses of covariance were carried. Women with the non-C allele showed significantly lower AIx@75 in participants aged <65years and baPWV in participants aged ≥65years than those with C allele. In contrast, men with the non-C allele showed significantly higher PP in participants aged <65years, and higher ACR and non-HDL-C/HDL-C ratio in participants aged ≥65years. In men on cholesterol-lowering medication, the non-C allele carriers showed significantly higher non-HDL-C compared to those in the C allele carriers. eNOS T-786C polymorphism is significantly associated with arteriosclerotic parameters accompanied with age and gender differences, possibly involving antioxidative and/or endothelial signaling other than inflammatory signaling.

Associations between nitric oxide synthase 3 gene polymorphisms and preeclampsia risk: a meta-analysis.

Previous studies have examined the role of three NOS3 gene polymorphisms [G894T, T-786C, and the variable number of tandem repeats 4b/a (VNTR 4b/a)] in the susceptibility to preeclampsia with inconclusive findings. We therefore conducted an updated meta-analysis by including more studies. The most appropriate genetic model was chosen for each polymorphism by using a well-established method. Pooled results indicated that, compared with the GT + GG genotype, the TT genotype of G894T was associated with an increased risk of preeclampsia (odds ratio (OR) = 1.46; 95% confidence interval (CI) = 1.21–1.77, P < 0.001; I2 = 40.2%). The CC genotype of T-786C was also associated with a higher risk of preeclampsia (OR = 1.30; 95% CI = 1.07–1.58, P = 0.034; I2 = 46.9%) than the CT + TT genotype. No association was found for VNTR 4b/a. Stratified analysis indicated that the increased risk was evident for high-quality studies both for G894T and T-786C, and for studies conducted among Caucasians and Africans for T-786C. However, the increased risk for T-786C among Africans needs further confirmation due to the high probability of false-positive reports. Our results suggested that G894T and T-786C polymorphisms, but not VNTR 4b/a, were associated with an increased risk of preeclampsia.

The Relationship Between Endothelial Nitric Oxide Synthase Gene (NOS3) Polymorphisms, NOS3 Expression, and Varicocele.

Varicocele is an abnormal enlargement of the pampiniform venous plexus in the scrotum. Varicocele is the most common cause of secondary male infertility. Nitric oxide (NO), which has a role on varicocele pathophysiology, is synthesized by endothelial nitric oxide synthase gene (NOS3). In our study, we aimed to explain the relationship between varicocele, three common NOS3 polymorphisms (T-786C, G894T, 4b/a), and NOS3 mRNA expression levels. We investigated NOS3 T-786C, G894T, and 4b/a polymorphisms in 102 patients with varicocele and 100 healthy controls. Twenty-four patients and 17 controls were chosen for expression studies based on polymorphism subgroupings. Subgroup 1 includes patients who have no minor allele polymorphisms, and subgroups 2, 3, and 4 have T-786C, G894T, and 4b/a polymorphisms, respectively. The 4b/a polymorphism demonstrated significantly elevated levels in both allele and genotype analysis in the control group compared to the patient group. The G894T polymorphism was statistically elevated for genotypic frequencies in the patient group compared to the control group, but this finding did not extend to allelic frequencies. There were no statistically significant differences in either the allelic or genotypic frequencies between patients and control groups for the T-786C polymorphism. When patient and control expression levels were compared without considering the subgroups, the NOS3 expression level was found to be statistically higher in the patient group. There were no statistically significant differences in the patient and control group expression levels when stratified by subgroup, nor was there any effect of the polymorphisms under study on expression levels. The 4b/a polymorphism may have a protective effect for varicocelem and G894T polymorphism may contribute to varicocele occurrence by lowering the level of NO. The higher NOS3 expression levels in the patient group may be a kind of dilator compensatory mechanism to protect vascular anatomy in varicocele.