Polymorphisms in androgen metabolism genes with serum testosterone levels and prognosis in androgen-deprivation therapy

ObjectiveAndrogen metabolism is a key component in therapeutic resistance to androgen deprivation therapy (ADT). This study aimed to reveal the significance of genetic polymorphisms in genes involved in androgen metabolism, including CYP17A1, AKR1C3, and HSD17B, on serum testosterone levels during ADT, as well as the prognosis of men undergoing ADT for metastatic prostate cancer (CaP).Materials and methodsThis study included 104 Japanese patients with metastatic CaP, for whom serum testosterone data during ADT were available for 80 patients. The association of CYP17A1 (rs743572), AKR1C3 (rs12529), HSD17B1 (rs605059), HSD17B3 (rs2066479), and HSD17B4 (rs7737181) with serum testosterone levels during ADT and prognosis (progression-free survival and overall survival) was examined. Enzymatic activity in AKR1C3 H5Q was examined using recombinant protein.ResultsHomozygous wild-type (GG allele; median [interquartile range], 12.0 ng/ml [8.0–19.0 ng/ml]) AKR1C3 rs12529 was associated with higher serum testosterone levels during ADT compared with variant-type (GC/CC alleles; median [interquartile range], 9.0 ng/ml [6.4–10.8 ng/ml]). Consistently, variant-type (GC/CC alleles) AKR1C3 rs12529 showed significantly lower risk of progression (hazard ratio [95% confidence interval], 0.47 [0.24–0.96], P = 0.039) compared with homozygous wild-type (GG allele) on multivariate analysis. Meanwhile, other genetic variations were associated with neither serum testosterone during ADT nor prognosis. Enzyme activity of wild-type AKR1C3 was comparable to the H5Q mutant.ConclusionsTaken together, this study demonstrated that AKR1C3 polymorphism, which was associated with serum testosterone levels during ADT, may be a prognostic factor of the progression to castration-resistant prostate cancer in Japanese men with metastatic CaP.     

Polymorphism in autophagy gene ATG2B is not associated with bladder cancer recurrence after intravesical Bacillus Calmette-Guerin (BCG) immunotherapy in Asian patients

ObjectivesOptimal patient stratification is critical in the era of personalized medicine. Germline polymorphisms play an important role in the treatment response of various human diseases, including bladder cancer. Intravesical BCG therapy is widely-used for bladder cancer. However, tumor recurrence and progression are very common. Stratification based on germline polymorphisms may contribute to circumvent this clinical challenge. Autophagy pathway plays an important role in the nonspecific protective effects of BCG. Patients that carry C allele of rs3759601 in autophagy gene ATG2B showed increased risk of recurrence and progression in European population. We thus sought to analyze rs3759601 and its relevance in BCG response in Asian NMIBC patients.MethodFunctional impact of rs3759601 ATG2B (p.Gln1383Glu) was analyzed by bioinformatics programs including NCBI Conserved Domain Search, Clustal Omega, Polyphen and SIFT. NMIBC patients who received intravesical BCG at multiple hospitals in Singapore from 1995 to 2016 were included. These patients were genotyped for rs3759601 using high resolution melt analysis. The rs3759601 polymorphism was studied in correlation with the bladder cancer recurrence rate and disease progression rate in our cohort. Statistical analysis was conducted using Kaplan-Meier plots and the Chi-squared analysis.ResultsIn total, 307 individules were included in the study including 161 NMIBC patients and 146 healthy controls, predominately Chinese. The rs3759601 genotype distributions in our NMIBC patients were (GG 72.1%; GC 27.9%; CC 0%), which were distinct from the Dutch report (GG 32.8%; GC 47.4% and CC 19.8%, Buffen K et al, 2014). Consistently, the C allele frequencies of rs3759601 are 0.171 in our controls and 0.177 in East Asians from 1,000 Genome, but 0.406 in Europeans from 1,000 Genome. In silico analysis suggested rs3759601 ATG2B (p.Gln1383Glu) alteration is unlikely to be functionally deleterious. Statistical analysis revealed no significant association between ATG2B rs3759601 C allele and risk of bladder cancer recurrence (P= 0.353, GC vs. GG: hazard ratio [HR]= 1.324), or cancer progression (P= 0.454, GC vs. GG: HR = 0.658).ConclusionIn contrast to European NMIBC patients, ATG2B rs3759601 C allele is much less common in Asians and it not associated with BCG response in Asian NMIBC patients.     

TIMP2 Polymorphisms Association With Curve Initiation and Progression of Thoracic Idiopathic Scoliosis in the Caucasian Females

Idiopathic scoliosis (IS) etiology remains unclear, but strong genetic background is suggested. Previously reported TIMP2 study indicates an association of genic rs8179090 with IS progression in a Han Chinese population. However, there has been a lack of investigation into intragenic TIMP2 polymorphisms in IS patients. We recruited 100 Caucasian females with IS and 100 controls. Patients were subdivided accordingly to: progression rate, curve severity, joint mobility, and curve pattern. Allele‐specific‐polymerase chain reaction based on fluorescence resonance energy transfer was applied to evaluate nine TIMP2 polymorphisms. Distribution of genotype and allele frequency in only one polymorphism (rs11658743) differed in case–control study. Four of the polymorphisms (rs2277700, rs11077401, rs2376999, and rs4789934) showed non‐equal distributions either in genotype or/and allele distributions in the patients of different progression rates. The rs11077401 was related to curve severity patients distinction and the rs8179090 distinguished patients with different joint mobility level. Two polymorphisms either differed statistically in case of curve patterns subgrouping (rs8068674 and rs8179090) or showed a slight tendency toward significance in the recessive model of allele distributions (rs9916809 and rs8179090). The remaining two polymorphisms (rs2377005, rs11658743) showed no association with either clinical or radiographic IS characteristics. The influence of the G allele of the rs8179090 on the clinical course of IS has not yet been confirmed. We identified four TIMP2 polymorphisms (rs11077401, rs2376999, rs2277700, and rs4789934) that were associated with a higher risk of the progressive IS form. Further genetic association studies based on suggested clinical criteria would be necessary to validate TIMP2 polymorphisms associated with the curve progression. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2217–2225, 2019     

Association of mannan-binding lectin gene polymorphisms withprogression of severe lupus nephritis

Objective To investigate the association of single nucleotide polymorphisms (SNPs) of the mannan-binding lectin (MBL) gene with serum levels, development, progression and prognosis ofsevere lupus nephritis (LN). Methods A total of 107 severe lupus nephritis patients were enrolled in the study from January 2003 to October 2013. Integrated capillary electrophoresis was used to detect MBL gene polymorphism in peripheral blood DNA. ELISA was used to detect serum MBL concentration. Kaplan-Meier survival analysis was used to analyse the relationship of renal function, kidney prognosis with the gene polymorphism of rs11003125. Cox regression model analysis was used to identify possible risk factors of kidney prognosis. Results SNPs in rs11003125, rs7096206, rs7095891 and rs1800450 were found. The serum MBL concentration of patients with GG genotype in rs11003125 was higher than that with GC genotype, and both were higher than that with CC genotype (P＜0.01). Patients with SNP of rs11003125 had higher systolic blood pressure, diastolic blood pressure, mean arterial pressure, serum creatinine, urea nitrogen, 24 hours urinary protein, and lower glomerular filtration rate, shorter mean renal survival time (P＜0.05). Progressive severe LN patients had higher GC+CC (91.9% vs 75.7%, P＝0.041), CT+TT（32.4% vs 14.3%, P＝0.027） genotype frequencies at promoter rs11003125 and rs7095891, respectively, compared with that of non-progressive severe LN patients. Conclusions rs11003125, rs7096206 and rs1800450 polymorphisms of MBL gene are associated with lower serum MBL levels in severe LN patients. rs11003125 promoter polymorphisms of MBL gene may contribute to the onset severity, progression and prognosis of severe lupus nephritis.     

Toll-like receptor 9 SNPs are susceptible to the development and progression of membranous glomerulonephritis: 27 years follow-up in Taiwan

Abstract

The purpose of this study was to determine whether toll-like receptors 9 (TLR9) gene polymorphisms (rs352139 and rs352140) were markers of susceptibility to the development and progression of membranous nephropathy (MGN) in Taiwanese patients. The polymorphisms were investigated by polymerase chain reaction in 397 Taiwanese individuals (134 MGN patients and 263 controls). Patients with malignancy, chronic infectious diseases, lupus nephritis, or drug-induced secondary MGN were excluded from the study. Data showed AA genotype at rs352139 SNP or GG genotype at rs352140 SNP may indicate higher risk for MGN (odds ratio [OR]?=?1.55; 95% confidence interval [CI]?=?1.02–2.35, at rs352139 SNP; OR?=?1.57; 95% CI?=?1.03–2.39, at rs352140 SNP). However, MGN patients with A–G haplotype were susceptible for decreased creatinine clearance rate and for seriously tubule-interstitial fibrosis. The result suggests for the first time that TLR9 (rs352139 and rs352140) polymorphisms may contribute to the development and progression of MGN.     

VAV1 Gene Polymorphism is Associated With Kidney Allograft Rejection

BackgroundVAV1 is an intracellular signal transduction protein that plays a significant role in signal transduction in T cells. Several studies suggest that VAV1 signaling plays significant roles in allograft rejection. The aim of this study was to examine the association between VAV1 gene polymorphisms and renal allograft function.MethodsThe study included 270 patients after allograft renal transplantation. We examined the associations between VAV1 gene polymorphisms and complications after transplantation, such as delayed graft function, acute rejection, and chronic allograft dysfunction.ResultsThere were no statistically significant associations between VAV1 genotypes and delayed graft function and chronic allograft dysfunction. Among patients with acute allograft rejection, we observed decreased frequencies of VAV1 rs2546133 TT and CT genotypes (P = .03) and T allele (P = .02), as well as VAV1 rs2617822 GG and AG genotypes (P = .05) and G allele (P = 0.04). In the multivariate regression analysis, the higher number of VAV1 rs2546133 T alleles showed a protective effect against the acute rejection in kidney allograft recipients.ConclusionsThe results of our study suggest that polymorphisms in the VAV1 gene are associated with kidney allograft rejection.     

Matrix metalloproteinase-2 polymorphism is associated with prognosis in prostate cancer

ObjectiveProstate cancer (PCa) is the most frequent tumor in males in Brazil. Single nucleotide polymorphisms (SNP) have been demonstrated in the promoter region of matrix metalloproteinases (MMPs) genes and have been associated with development and progression of some cancers. In this study, our aim was to investigate a possible relation between polymorphism of the promoter region of the MMP2 gene and classical prognostic parameters in prostate cancer.Materials and methodsGenomic DNA was extracted using conventional protocols. The DNA sequence containing the polymorphic site was amplified by real-time polymerase chain reaction, using fluorescent probes (TaqMan).ResultsIn patients with tumors of a higher stage (pT3), a polymorphic allele in the MMP2 gene was more frequent (P = 0.026) than in patients with lower tumor stage. A polymorphic allele in the MMP2 gene was more frequent in Gleason ≥ 7 than in Gleason ≤ 6 (P = 0.042).ConclusionsWe conclude that MMP2 polymorphism can be used together with pathological stage and Gleason score to identify patients with worse prognosis. Our results illustrate the potential use of MMP2 SNP as a molecular marker for prostate cancer.     

Hypoxia and renal cell carcinoma: The influence of HIF1A+1772C/T functional genetic polymorphism on prognosis

Objectives

Hypoxia-inducible factor (HIF-1) is a key regulator of the genes involved in the cellular response to hypoxia. Overexpression of HIF-1 has been implicated in the pathogenesis of renal cell carcinoma (RCC), and functional polymorphisms of the HIF1A gene may confer susceptibility to RCC. Our purpose was to assess the influence of HIF1A+1772C/T (rs11549465) polymorphism on RCC prognosis.

Analysis of risk factors and prognostic factors for gastrointestinal stromal tumors with gastrointestinal hemorrhage: Based on propensity score matching method

BackgroundThis study aimed to analyze the relationship between risk factors and prognosis of patients with gastrointestinal stromal tumor associated with gastrointestinal bleeding.MethodsAccording to whether there was gastrointestinal bleeding, 246 patients with gastrointestinal stromal tumors were divided into 2 groups. The clinicopathological baseline characteristics of the 2 groups of patients were balanced by propensity score matching, and the Kaplan-Meier method was used to draw the survival curve and analyze the overall survival of the 2 groups of patients. The receiver operating characteristic curve was drawn to evaluate the accuracy of Modified National Institutes of Health criteria and Armed Forces Institute of Pathology criteria in predicting the prognosis and postoperative recurrence of patients. Logistic regression analysis of risk factors affecting gastrointestinal stromal tumor with gastrointestinal bleeding before matching. Univariate and multivariate analyses of risk factors affecting the prognosis of patients with gastrointestinal stromal tumors after matching were performed using Cox regression models.ResultsBefore matching, the accuracy of Modified National Institutes of Health criteria in predicting postoperative survival status and recurrence was higher than that of Armed Forces Institute of Pathology criteria. Modified National Institutes of Health criteria and relapse were the risk factors for gastrointestinal stromal tumor with gastrointestinal bleeding independent risk factors (P < .05). After 1:1 matching, the general clinical data of patients with gastrointestinal bleeding group and nongastrointestinal bleeding group were balanced (P > .05). The results of matched survival analysis indicated that tumor location and gastrointestinal bleeding were independent risk factors for the prognosis of patients with gastrointestinal stromal tumors (P < .05). The results of subgroup analysis according to anatomical site showed that there was no significant difference between the gastrointestinal bleeding group and the nongastrointestinal bleeding group (P > .05). Survival analysis showed that patients with gastrointestinal stromal tumors with gastrointestinal bleeding had a worse prognosis, and the results were also applicable in different tumor anatomical locations and different Modified National Institutes of Health criteria.ConclusionModified National Institutes of Health criteria and relapse are independent risk factors for gastrointestinal stromal tumors with gastrointestinal bleeding; gastrointestinal bleeding is associated with poor prognosis in patients with gastrointestinal stromal tumors, and patients with gastrointestinal stromal tumors with gastrointestinal bleeding have a worse prognosis.     

Association of chromosomal locus 8q24 and risk of prostate cancer: a hospital-based study of German patients treated with brachytherapy

BackgroundGenetic susceptibility contributes to the risk of prostate cancer but the underlying genes are largely unknown. Polymorphic loci on chromosome 8q24 have emerged as possible risk factors for breast and prostate cancer from genome-wide association studies.ObjectiveWe aimed to define the risks associated with two single nucleotide polymorphisms, rs1447295 and rs13281615, in a hospital-based series of prostate cancer patients treated with brachytherapy.Material and methodsWe analyzed genomic DNA samples of 488 prostate cancer cases undergoing brachytherapy at Hannover Medical School, and of 462 male controls from the same location. Genotyping was performed using 5′-exonuclease allelic discrimination assays, and results were evaluated with χ² tests and logistic regression analyses.ResultsWe investigated whether rs1447295 and rs13281615 are associated with disease risk in a hospital-based prostate cancer case-control series from Northern Germany. The rare allele of rs1447295 was observed at higher frequency among cases than among hospital-based controls (13.9% vs. 10.2%, P = 0.01), and there was a dose-dependent trend towards a higher prevalence of heterozygous and homozygous carriers among the prostate cancer patients (per allele OR 1.42, 95% CI 1.07; 1.87, P = 0.02). By contrast, the rare allele of rs13281615 did not predispose to prostate cancer (per allele OR 0.84, 95% CI 0.70; 1.00, P = 0.05). The distribution of combined 8q24 genotypes was significantly different between cases and controls (P = 0.01).ConclusionOur results corroborate previous reports of 8q24 as a prostate cancer susceptibility locus and provide evidence for rs1447295 as a potentially important genetic marker. Further studies are required to confirm whether the adjacent breast cancer-associated variant rs13281615 may be inversely associated with prostate cancer risk.     

Genetic risk factors for post-transplantation diabetes mellitus in Chinese Han renal allograft recipients treated with tacrolimus

BackgroundPost-transplantation diabetes mellitus (PTDM) is a serious metabolic complication after kidney transplantation. The aim of this study was to explore the association of clinical variables and five selected single nucleotide polymorphisms (SNPs) with PTDM in Chinese Han renal allograft recipients taking tacrolimus (TAC).MethodsA total of 129 non-diabetic, primary, Chinese Han renal allograft recipients treated with TAC were enrolled. Five SNPs (CYP3A5 rs776741, rs776746, rs15524, CYP24A1 rs2296241, and PPARG rs1801282) were genotyped and analyzed.ResultsAmong 129 recipients, 17 (13.2%) developed PTDM. Both univariate and multivariate analysis demonstrated that age over 50 years old and CYP24A1 rs2296241 A allele were independently correlated with the development of PTDM, while no significant differences was observed in TAC pharmacokinetics and CYP3A5, PPARG polymorphisms between two groups.ConclusionsPatients with advanced age and CYP24A1 rs2296241 A allele had an increased risk of PTDM after kidney transplantation.     

The Prognostic Significance of Metastatic Perivesical Lymph Nodes Identified in Radical Cystectomy Specimens for Transitional Cell Carcinoma of the Bladder

PurposeWe determined the prognostic significance of metastatic perivesical lymph nodes (PVLN) in transitional cell carcinoma of the bladder (TCC).Materials and MethodsA retrospective review of 198 consecutive patients who underwent radical cystectomy for clinically organ confined TCC identified 32 patients with PVLN in pathology specimens. Patient characteristics were compared. Overall survival, disease-specific survival (DSS) and disease-free survival were estimated using Kaplan-Meier actuarial methodology. The log-rank test was used to compare the differences between patients with and without metastatic TCC to PVLN. Cox multivariate regression analysis was used to determine whether the effect of metastatic PVLN on survival was independent of pathological stage.ResultsMetastatic TCC was found in the PVLN of 14 patients. Median followup and age were 13.5 months and 66.5 years, respectively. Patients with and without metastatic PVLN had similar characteristics and pathological disease staging. The overall survival, DSS and disease-free survival were significantly less for patients with metastatic TCC in PVLN (p = 0.002, p = 0.013 and p <0.001, respectively), and involvement of PVLN and pelvic nodes (p = 0.001, p = 0.010 and p = 0.041, respectively). Metastatic PVLN was an independent predictor of OS and DSS (p = 0.016 and p = 0.025, respectively).ConclusionsMetastases to PVLN appear to confer a significantly worse prognosis for patients undergoing radical cystectomy. Patients with identifiable metastatic PVLN may benefit from early adjuvant therapies.     

Nuclear Factor Erythroid-2-related Factor 2 Gene Polymorphisms in Vitiligo

BackgroundOxidative stress is now one of the accepted theories of vitiligo development. Nuclear factor erythroid-2-related factor 2 (Nrf2) regulates the expression of antioxidant proteins.ObjectiveThis work aimed to evaluate the association of Nrf2 gene polymorphisms with the susceptibility to vitiligo among a sample of Egyptian patients with vitiligo.MethodsThis case-control study included 100 patients with vitiligo and 50 healthy matched volunteers serving as a control group. Genotyping was carried out by real-time polymerase chain reaction.ResultsThe frequencies of TT, CT, and combined (TT+CT) genotypes and the T allele of Nrf2 (rs35652124) were significantly increased in the studied patients with vitiligo relative to the healthy controls (p<0.001, p=0.012, p<0.001 and p<0.001, respectively). There was a nonsignificant difference between patients and controls regarding Nrf2 (rs6721961) genotypes. However, the T allele of Nrf2 (rs6721961) was significantly predominant in the studied patients compared to in the controls (p=0.029). Among the studied criteria, the T allele of Nrf2 (rs6721961) was predominant in patients with a marginal type of repigmentation (p=0.022), while the G allele of the same single-nucleotide polymorphism was associated with a higher body mass index value (p=0.034). One hundred percent of patients with vitiligo with the Nrf2 (rs6721961) GT genotype had a progressive disease course (p=0.015).ConclusionNrf2 (−617 T/G) and (−653 T/C) polymorphism might play a role in patient susceptibility to vitiligo and modify the clinical presentation of the disease.     

The TERT locus genotypes of rs2736100-CC/CA and rs2736098-AA predict shorter survival in renal cell carcinoma

Objectives

The single nucleotide polymorphisms (SNPs) at the TERT rs2736100 and rs2736098 are associated with multicancer susceptibility, however, published findings regarding renal cell carcinoma (RCC) risk are conflicting. In addition, the potential of these SNPs to predict outcomes in RCC remains unclear. The present study is designed to address these questions.

Comparison of the prognosis of primary vs. progressive muscle invasive bladder cancer after radical cystectomy: Results from a large multicenter study

PurposeTo assess whether progressive and primary muscle invasive bladder cancer (MIBC) have different prognosis after radical cystectomy or not. To date only a few data are available on this topic with conflicting results. Further studies on large cohort are needed to clarify these outcomes that may influence bladder cancer management for these patients.Material and methodsA multicentre retrospective study was conducted on patient treated for MIBC at 5 centres between 2005 and 2015 by radical cystectomy. Patients’ outcomes were compared between patients with primary MIBC vs. progressive MIBC subsequent to a history of non-muscle invasive bladder cancer (NMIBC).ResultsA total of 1197 patients were included. Median (IQ) age was 65 (58–72) years and median follow-up was 65 months. Baseline characteristics were similar between the groups as well as the Tumour pT stage, N status and positive surgical margins. Patients with progressive MIBC had worse overall survival (OS) (hazard ratio [HR] 1.36, [95%CI 1.10–1.76]; P = 0.004), cancer specific survival (CSS) (HR 1.41 [1.13–1.78]; P = 0.002), and recurrence-free survival (RFS) (HR 1.21 [1.01–1.49]; P = 0.05). Pathological stage ≥pT3, positive surgical margins, and positive lymph nodes status (pN+) were also found as predictors of OS, CSS, and RFS.ConclusionsOur results suggest that patient having a progressive BC have a worse prognosis in terms of OS, PFS, and CSS than patient with primary disease. These 2 groups may require different management and patients with high risk NMIBC should be assessed properly to avoid progression and be offered early cystectomy.     

ErbB4 receptor polymorphism 2368A>C and risk of breast cancer

PurposeA number of single nucleotide polymorphisms (SNPs) in EebB4 gene have been studied, which has clarified their impact on breast cancer in different populations. Nevertheless, the importance of rs13423759 in breast cancer has not been studied and its effect remained almost unclear. In this paper, we evaluated the frequency of rs13423759 different alleles in Iranian population and statistically analyzed their association with breast cancer risk.Materials and methodsAllele-specific Primer PCR (ASP-PCR) was recruited in this study to genotype rs13423759 position in 172 breast cancer and 148 healthy control subjects. The genotypes of control and cases were analyzed statistically to find the association between rs13423759 alleles and breast cancer incidence and its clinicopathological characteristics. In silico studies were performed in order to find the mechanistic viewpoint of rs13423759 alleles in breast cancer.Resultsrs13423759 allele C was shown to be significantly associated with breast cancer risk, HER2 positivity and increased risk of metastasis. Reciprocally, allele A was correlated with the lowered risk of breast cancer. The in silico studies showed that rs13423759 allele C is capable to strengthen the interaction between miR-548as, an oncomiRNA, and ErbB4 mRNA, leading to its lowered concentration in the cells.Conclusion: rs13423759 allele C is significantly associated with the enhanced risk of breast cancer, elevated metastasis and HER2 positivity.     

Role of the FKBP5 polymorphism rs1360780, age,sex, and type of surgery in weight loss after bariatric surgery: a follow-up study

BackgroundEmerging evidence suggests that the FK506 binding protein 51 (FKBP5/FKBP51), encoded by the FKBP5 gene, influences weight and metabolic regulation. The T allele of a functional polymorphism in FKBP5 (rs1360780), has been associated with the expression of FKBP51 and weight loss after bariatric surgery.ObjectiveTo examine the role of the FKBP5 rs1360780 polymorphism in relation to age, sex, and type of surgery in weight loss after bariatric surgery in patients with severe obesity.SettingUniversity Hospital in SpainMethodsA cohort of 151 obese patients submitted to Roux-en-Y gastric bypass (62.3%) and sleeve gastrectomy (37.7%) were followed-up during 24-months (t_24m; loss to follow-up: 0%). During the postoperative period body mass index (BMI) and percentage of excess and total weight loss were evaluated.ResultsThe BMI analysis showed an effect of the interaction FKBP5 genotype by sex (P = .0004) and a tendency to the interaction genotype by surgery (P = .048), so that men carrying the T allele had higher BMI at t_24m than those without the T allele, and T-allele carriers that underwent sleeve gastrectomy had higher BMI at t_24m than the noncarriers. Additionally, we found an interaction between FKBP5 and age for the percentage of excess weight loss and BMI (P = .0005 and P = 1.5e−7, respectively), whereby individuals >48 years with the T allele displayed significant differences for the analyzed variables at t_24m compared with the homozygotes for the alternate C allele showing lower weight loss.ConclusionFKBP5 rs1360780 genotype has specific effects on weight loss outcomes after bariatric surgery depending on sex, age, and type of surgery, suggesting worse results in older males carrying the T allele who have undergone sleeve gastrectomy.     

Manganese superoxide dismutase,glutathione peroxidase and catalase gene polymorphisms and clinical outcomes in acute kidney injury

Introduction The aim of this study was to evaluate the potential association of single gene polymorphisms of manganese superoxide dismutase (MnSOD), glutathione peroxidase 1 (GPX1) and catalase (CAT) with clinical outcomes of acute kidney injury (AKI). Materials and methods Ninety AKI patients and 101 healthy volunteers were included in the study. Determination of MnSOD rs4880, GPX1 rs1050450 and CAT rs769217 polymorphisms was performed using real-time polymerase chain reaction amplification. The duration of hospitalization of AKI patients, dialysis and intensive care requirements, sepsis, oliguria and in-hospital mortality rates were assessed. Results The MnSOD, GPX1 and CAT genotypes and allele frequencies of AKI patients did not differ significantly from those of healthy controls. In patients with a T allele in the ninth exon of the CAT gene, intensive care requirements were greater than those of patients with the CC genotype (p?=?0.04). In addition, sepsis and in-hospital mortality were observed significantly more frequently in patients with a T allele in the ninth exon of the CAT gene (p?=?0.03). Logistic regression analysis determined that bearing a T allele was the primary determinant of intensive care requirements and in-hospital mortality, independent of patient age, gender, presence of diabetes and dialysis requirements (OR 6.10, 95% CI 1.34–27.81, p?=?0.02 and OR 10.25, 95% CI 1.13–92.80, p?=?0.04, respectively). Conclusion Among AKI patients in the Turkish population, hospital morbidity and mortality were found to be more frequent in patients bearing a T allele of the rs769217 polymorphism of the CAT gene.