Correlations of MTHFR 677C>T Polymorphism with Cardiovascular Disease in Patients with End-Stage Renal Disease: A Meta-Analysis

ObjectiveThis meta-analysis was conducted to evaluate the correlations of a common polymorphism (677C>T) in the methylenetetrahydrofolate reductase (MTHFR) gene with risk of cardiovascular disease (CVD) in patients with end-stage renal disease (ESRD).MethodThe following electronic databases were searched without language restrictions: Web of Science (1945∼2013), the Cochrane Library Database (Issue 12, 2013), MEDLINE (1966∼2013), EMBASE (1980∼2013), CINAHL (1982∼2013) and the Chinese Biomedical Database (CBM) (1982∼2013). Meta-analysis was performed using STATA statistical software. Odds ratios (ORs) with their 95% confidence intervals (95%CIs) were calculated.ResultsEight cohort studies met all inclusion criteria and were included in this meta-analysis. A total of 2,292 ESRD patients with CVD were involved in this meta-analysis. Our meta-analysis results revealed that the MTHFR 677C>T polymorphism might increase the risk of CVD in ESRD patients (TT vs. CC: OR = 2.75, 95%CI = 1.35∼5.59, P = 0.005; CT+TT vs. CC: OR = 1.39, 95%CI = 1.09∼1.78, P = 0.008; TT vs. CC+CT: OR = 2.52, 95%CI = 1.25∼5.09, P = 0.010; respectively). Further subgroup analysis by ethnicity suggested that the MTHFR 677C>T polymorphism was associated with an elevated risk for CVD in ESRD patients among Asians (TT vs. CC: OR = 3.38, 95%CI = 1.11∼10.28, P = 0.032; CT+TT vs. CC: OR = 1.44, 95%CI = 1.05∼1.97, P = 0.022; TT vs. CC+CT: OR = 3.15, 95%CI = 1.02∼9.72, P = 0.046; respectively), but not among Africans or Caucasians (all P>0.05).ConclusionOur findings indicate that the MTHFR 677C>T polymorphism may be associated with an elevated risk for CVD in ESRD patients, especially among Asians.     

A Meta-Analysis of Mortality in End-Stage Renal Disease Patients Receiving Implantable Cardioverter Defibrillators (ICDs)

Data on the effectiveness of implantable implantable cardioverter defibrillators (ICDs) with respect to reducing mortality in patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) are lacking. The purpose of this meta-analysis was to compare the mortality of patients with ESRD who have received and not received an ICD. A search was conducted on January 31, 2013 of Medline, Cochrane, EMBASE, and Google Scholar. Studies were selected for inclusion based on the following criteria. 1) Randomized controlled trial. 2) ESRD patients with heart failure. 3) Device therapy (ICD, CRT-defibrillator [CRT-D]) used to treat heart failure. 4) Primary outcome is survival analysis. 5) Retrospective study if survival analysis was performed. The primary outcome was overall survival (OS), and the secondary outcome was 2-year survival. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated, and a χ²-based test of homogeneity was performed. Three studies were included in the analysis. The combined OR for OS was 2.245 (95% CI 1.871 to 2.685, P<0.001), indicating that patients with an ICD had a significantly higher OS than those without an ICD. The combined OR for 2-year survival was 2.312 (95% CI 1.921 to 2.784, P<0.001), indicating that patients with an ICD had a significantly higher 2-year survival rate than those without an ICD. The use of ICD in patients with ESRD is associated with an increase in the OS and the 2-year survival rate.     

Negative Interference by Rheumatoid Factor of Plasma B-Type Natriuretic Peptide in Chemiluminescent Microparticle Immunoassays

Background

The chemiluminescent microparticle immunoassay (CMIA) is widely used for the quantitative determination of B-type natriuretic peptide (BNP) in human ethylenediaminetetraacetic acid plasma. Rheumatoid factor (RF) is usually thought to result in a positive interference in immunoassays, but it is not clear whether its presence in plasma can lead to interferences in the CMIA of BNP.

Methods

The estimation of BNP recovery was carried out by diluting high-concentration BNP samples with RF-positive or RF-negative plasma at a ratio of 1∶9. The diluted samples were then tested using the ARCHITECT i2000 System and ARCHITECT BNP Reagent Kits and the recovery was then calculated.

Results

When the RF level ranged from 48 to 1420 IU/mL, the average recovery of BNP was 79.29% and 91.61% in the RF-positive and RF-negative plasma samples, respectively, and was thus significantly lower in the group of RF-positive plasma samples than in the group of RF-negative plasma samples. At a dilution of 1∶16, the measured BNP level increased by >36% in six of the seven RF-positive plasma samples. The recovery of BNP increased significantly in the RF-positive plasma samples after pretreatment with IgG-sensitive latex particles. In addition, The BNP recovery was not significantly related to the plasma RF at concentrations ranging from 48 to 2720 IU/mL.

Conclusions

Measurement of BNP by CMIA is susceptible to interference from RF leading to predominantly (but not exclusively) lower results. Pretreatment of samples with blocking reagents is advisable prior to the initiation of denying patient''s necessary treatment.     

Changes of Plasma B-Type Natriuretic Peptide Levels after High-Pressure Post-Dilation following Coronary Stent Deployment

Objective

To evaluate the changes of plasma B-type natriuretic peptide(BNP) levels after high-pressure post-dilation following coronary stent deployment.

Methods

A total of 173 patients undergoing percutaneous coronary intervention for the left anterior descending artery were enrolled into the study. All patients were divided into two groups: the conventional group and the post-dilation group. The plasma BNP, troponin I(TnI), myocardial band isoenzyme of creatine kinase(CK-MB) levels and the serum high sensitive C-reactive protein(hs-CRP) levels immediately before and 24 hours after the interventional procedures were compared between the two groups.

Results

There were no significant differences between the two groups in terms of clinical features, clinical and biochemical parameters, stent parameters, pre-procedural plasma BNP and TnI levels, pre-procedural serum hs-CRP levels, as well as pre- and post-procedural CK-MB levels (all P>0.05). In the conventional group, post-procedural plasma BNP levels were significantly reduced when compared with the pre-procedural levels, median(25th,75th) were 32.5 ng/L(15.0,52.4) vs. 37.7 ng/L(18.2,67.3), P = 0.001. In the post-dilation group, post-procedural plasma BNP levels were significantly increased when compared with the pre-procedural levels, median(25th,75th) were 53.5 ng/L(29.6,82.8) vs. 44.2 ng/L(17.15,70.7), P<0.0001. Post-procedural plasma TnI levels were also significantly increased when compared with the pre-procedural levels in both groups, median(25th,75th) were 0.02 ng/L(0.01,0.08) vs. 0.01 ng/L(0.01,0.01), 0.05 ng/L(0.01,0.35) vs. 0.01 ng/L(0.01,0.01), respectively, P<0.0001, so were the serum hs-CRP levels, median(25th,75th) were 3.3 mg/L(2.4,4.7) vs. 2.2 mg/L(1.4,3.3), 4.2 mg/L(3.175,5.825) vs. 2.3 mg/L(1.45,3.6), respectively, P<0.0001. Post-procedural plasma BNP, TnI and serum hs-CRP levels in the post-dilation group were significantly higher than those in the conventional group(all P<0.0001).

Conclusion

High-pressure post-dilation following coronary stent deployment resulted in a significant increase of plasma BNP levels, as well as plasma TnI levels and serum hs-CRP levels, which may be related to myocardial perfusion, more myocardial injury and more inflammation.     

血浆B 型脑钠肽对急性冠脉综合征的病情影响及预后评估

目的:探讨血浆B型脑钠肽(BNP)对急性冠脉综合征的病情影响及预后评估的作用,为临床实践提供参考.方法:分别对30例健康体检者(对照组)和81例ACS患者(观察组)检测其入院24小时内的血浆BNP浓度,并在住院一周内行冠状动脉造影术,检查病变的冠脉支数.结果:观察组的血浆BNP浓度高于对照(P＜0.01),病变动脉支数与BNP水平呈正相关(P＜0.01).结论:BNP是急性冠脉综合征发病的重要因素,其水平高低可反映病情的严重程度,是预测病情和预后的重要指标.临床上应有效的监测BNP水平,对正确诊断和有效治疗急性冠脉综合征具有重要的意义.     

急性心肌梗死患者脑钠肽水平与血管病变的关系

目的:探讨急性心肌梗死患者血浆脑钠肽(BNP)水平与梗死相关动脉及病变血管的关系。方法:选取2010.7-2011.7于上海市第一人民医院诊断为急性心肌梗死的患者。分为ST抬高型心梗患者和非ST抬高型心梗患者两组,比较BNP水平与血管病变的关系。结果:(1)两组患者的年龄、男女比例、高血压病与糖尿病患病率、吸烟患者比例之间无显著差异。NSTEMI患者中,既往心梗和既往经皮冠状动脉成形术(PTCA)的比例和左室射血分数明显高于STEMI患者。(2)NSTEMI患者多支血管病变比例显著高于STEMI患者并且梗死相关动脉为左回旋支(LCX)的比例显著高于STEMI患者。(3)病变血管支数与心梗患者BNP水平无关,STEMI患者左冠状动脉前降支(LAD)为IRA的患者BNP水平显著高于LCX和右冠状动脉(RCA)分别为IRA的患者。NSTEMI患者LAD、LCX和RCA分别为IRA的患者其BNP水平无显著差异。结论:STEMI患者前壁心梗BNP水平较高,NSTEMI患者BNP水平对血管病变支数和IRA无预测价值。     

Risk of End-Stage Renal Disease after Cancer Nephrectomy in Taiwan: A Nationwide Population-Based Study

BackgroundThe conclusions of population-based studies examining the risk of developing end-stage renal disease (ESRD) after nephrectomy among patients with renal cell carcinoma (RCC) remain inconclusive. In this study, we sought to examine whether patients with RCC undergoing radical nephrectomy (RN) have higher risk of ESRD compared to those undergoing partial nephrectomy (PN).MethodsNationwide population-based retrospective cohort of 7670 patients with RCC who underwent RN or PN between 2000 and 2011 as recorded in the Taiwan National Health Insurance in-patient claims data were analyzed. The primary outcome of interest was the occurrence of ESRD requiring regular renal hemodialysis. Multivariable Cox proportional hazard regression model was performed to assess the risk.FindingsThe median follow-up for the post-propensity matched cohort (1212 PN and 2424 RN) was 48 months. Seventy patients (2.9%) developed ESRD among those who underwent RN, for an incidence rate of 6.9 cases per 1000 person-years. In contrast, only 23 patients (1.9%) developed ESRD among patients who underwent PN, for an incidence rate of 5.5 cases per 1000 person-years. Despite the higher incidence rate of ESRD among RN, the aIRR (RN/PN) was 1.26 (95% CI 0.78-2.01), which was not statistically significant.ConclusionsThis Taiwan nationwide population-based study suggests that patients with RCC undergoing RN do not have significantly higher risk of developing ESRD compared to those undergoing PN.     

Effectiveness of Influenza Vaccination in Patients with End-Stage Renal Disease Receiving Hemodialysis: A Population-Based Study

Background

Little is known on the effectiveness of influenza vaccine in ESRD patients. This study compared the incidence of hospitalization, morbidity, and mortality in end-stage renal disease (ESRD) patients undergoing hemodialysis (HD) between cohorts with and without influenza vaccination.

Methods

We used the insurance claims data from 1998 to 2009 in Taiwan to determine the incidence of these events within one year after influenza vaccination in the vaccine (N = 831) and the non-vaccine (N = 3187) cohorts. The vaccine cohort to the non-vaccine cohort incidence rate ratio and hazard ratio (HR) of morbidities and mortality were measured.

Results

The age-specific analysis showed that the elderly in the vaccine cohort had lower hospitalization rate (100.8 vs. 133.9 per 100 person-years), contributing to an overall HR of 0.81 (95% confidence interval (CI) 0.72–0.90). The vaccine cohort also had an adjusted HR of 0.85 [95% CI 0.75–0.96] for heart disease. The corresponding incidence of pneumonia and influenza was 22.4 versus 17.2 per 100 person-years, but with an adjusted HR of 0.80 (95% CI 0.64–1.02). The vaccine cohort had lowered risks than the non-vaccine cohort for intensive care unit (ICU) admission (adjusted HR 0.20, 95% CI 0.12–0.33) and mortality (adjusted HR 0.50, 95% CI 0.41–0.60). The time-dependent Cox model revealed an overall adjusted HR for mortality of 0.30 (95% CI 0.26–0.35) after counting vaccination for multi-years.

Conclusions

ESRD patients with HD receiving the influenza vaccination could have reduced risks of pneumonia/influenza and other morbidities, ICU stay, hospitalization and death, particularly for the elderly.     

Prognosis of Differentiated Thyroid Carcinoma in Patients with Graves Disease: A Systematic Review and Meta-Analysis

Objective: It is still controversial whether differentiated thyroid carcinoma (DTC) in patients with Graves disease (GD) can be more aggressive than non-Graves DTC. We conducted a systematic review and meta-analysis to examine the association between GD and prognosis in patients with DTC.Methods: We comprehensively searched the databases of MEDLINE and EMBASE from inception to March 2019. We included published studies that compared the risk of mortality and prognosis between DTC patients with GD and those with non-GD. Data from each study were combined using the random-effects model.Results: Twenty-five studies from February 1988 to May 2018 were included (987 DTC patients with GD and 2,064 non-Graves DTC patients). The DTC patients with GD had a significantly higher risk of associated multifocality/multicentricity (odds ratio, 1.45; 95% confidence interval, 1.04 to 2.02; I², 6.5%; P =.381) and distant metastasis at the time of cancer diagnosis (odds ratio, 2.19; 95% confidence interval, 1.08 to 4.47; I², 0.0%; P =.497), but this was not associated with DTC-related mortality and recurrence/persistence during follow-up.Conclusion: Our meta-analysis demonstrates a statistically significant increased risk of multifocality/multicentricity and distant metastasis at the time of cancer diagnosis in DTC patients with GD than those without GD.Abbreviations: CI = confidence interval; DTC = differentiated thyroid carcinoma; GD = Graves disease; LN = lymph node; OR = odds ratio; PTC = papillary thyroid carcinoma; TC = thyroid carcinoma; TSAb = thyroid-stimulating antibody; TSH = thyroid-stimulating hormone     

The Plasma B-Type Natriuretic Peptide Levels Are Low in Males with Stable Ischemic Heart Disease (IHD) Compared to Those Observed in Patients with Non-IHD: A Retrospective Study

Objective

Although the plasma B-type natriuretic peptide (BNP) level is a marker of heart failure, it is unclear whether BNP per se plays a pivotal role for pathogenic mechanisms underlying the development of ischemic heart disease (IHD). In this study, we retrospectively examined the plasma BNP levels in stable patients with IHD and compared to stable patients with cardiovascular diseases other than IHD.

Methods

The study population was 2088 patients (1698 males and 390 females) who were admitted to our hospital due to IHD (n = 1,661) and non-IHD (n = 427) and underwent cardiac catheterization. Measurements of the hemodynamic parameters and blood sampling were performed.

Results

The plasma BNP levels were significantly lower in the IHD group than in the non-IHD group (p<0.001). The multiple regression analysis examining the logBNP values showed that age, a male gender, low left ventricular ejection fraction, low body mass index, serum creatinine, atrial fibrillation and IHD per se were significant explanatory variables. When the total study population was divided according to gender, the plasma BNP levels were found to be significantly lower in the IHD group than in the non-IHD group among males (p<0.001), but not females (p = NS). Furthermore, a multiple logistic regression analysis of IHD showed the logBNP value to be a significant explanatory variable in males (regression coefficient: −0.669, p<0.001), but not females (p = NS).

Conclusions

The plasma BNP levels were relatively low in stable patients with IHD compared with those observed in stable patients with non-IHD; this tendency was evident in males. Perhaps, the low reactivity of BNP is causally associated with IHD in males. We hope that this study will serve as a test of future prospective studies.     

Incidence of End-Stage Renal Disease in the Turkish-Cypriot Population of Northern Cyprus: A Population Based Study

Background

This is the first report of the incidence and causes of end-stage renal disease (ESRD) of the Turkish-Cypriot population in Northern Cyprus.

Methods

Data were collected over eight consecutive years (2004–2011) from all those starting renal replacement therapy (RRT) in this population. Crude and age-standardised incidence at 90 days was calculated and comparisons made with other national registries. We collected DNA from the entire prevalent population. As an initial experiment we looked for two genetic causes of ESRD that have been reported in Greek Cypriots.

Results

Crude and age-standardised incidence at 90 days was 234 and 327 per million population (pmp) per year, respectively. The mean age was 63, and 62% were male. The age-adjusted prevalence of RRT in Turkish-Cypriots was 1543 pmp on 01/01/2011. The incidence of RRT is higher than other countries reporting to the European Renal Association – European Dialysis and Transplant Association, with the exception of Turkey. Diabetes is a major cause of ESRD in those under 65, accounting for 36% of incident cases followed by 30% with uncertain aetiology. 18% of the incident population had a family history of ESRD. We identified two families with thin basement membrane nephropathy caused by a mutation in COL4A3, but no new cases of CFHR5 nephropathy.

Conclusions

This study provides the first estimate of RRT incidence in the Turkish-Cypriot population, describes the contribution of different underlying diagnoses to ESRD, and provides a basis for healthcare policy planning.     

The Risk of Peripheral Arterial Disease after Parathyroidectomy in Patients with End-Stage Renal Disease

PurposeThe changes of the risk of peripheral arterial disease (PAD) in patients with end-stage renal disease after parathyroidectomy are scant.MethodsWe used a nationwide health insurance claims database to select all dialysis-dependent patients with end-stage renal disease aged 18 years and older for the study population in 2000 to 2006. Of the patients with end-stage renal disease, we selected 947 patients who had undergone parathyroidectomy as the parathyroidectomy group and frequency matched 3746 patients with end-stage renal disease by sex, age, years since the disease diagnosis, and the year of index date as the non-parathyroidectomy group. We used a multivariate Cox proportional hazards regression analysis with the use of a robust sandwich covariance matrix estimate, accounting for the intra-cluster dependence of hospitals or clinics, to measure the risk of peripheral arterial disease for the parathyroidectomy group compared with the non-parathyroidectomy group after adjusting for sex, age, premium-based income, urbanization, and comorbidity.ResultsThe mean post-op follow-up periods were 5.08 and 4.52 years for the parathyroidectomy and non-parathyroidectomy groups, respectively; the incidence density rate of PAD in the PTX group was 12.26 per 1000 person-years, significantly lower than the data in the non-PTX group (24.09 per 1000 person-years, adjusted HR = 0.66, 95% CI = 0.46–0.94).ConclusionParathyroidectomy is associated with reduced risk of peripheral arterial disease in patients with end-stage renal disease complicated with severe secondary hyperparathyroidism.     

IgA Nephropathy Factors that Predict and Accelerate Progression to End-Stage Renal Disease

IgA nephropathy (IgAN) or Berger’s disease is a slowly progressing disease that leads to end-stage renal disease in 50 % of the patients within 25 years of the disease. However, several factors are associated with the accelerated progression of this disease causing early development of end-stage disease. Persistent proteinuria or hematuria, poorly controlled hypertension, elevated serum creatinine and prevalent glomerulosclerosis are some of the risk factors that expedite the deteriorative effects of IgAN. Thus, the progression of the disease can be delayed if the associated risk factors are handled and addressed in the nick of time.     

The Difference in Prognosis between Renal Sinus Fat and Perinephric Fat Invasion for pT3a Renal Cell Carcinoma: A Meta-Analysis

Background

In the current Tumour-Node-Metastasis (TNM) classification system for renal cell carcinoma (RCC), both renal sinus fat invasion (SFI) and perinephric fat invasion (PFI) are defined as T3a, suggesting that the prognosis should be similar for the two pathologic findings. Several studies, however, have reported a worse prognosis for SFI in patients with a T3a tumor. In order to compare the prognosis of these two pathologic findings (SFI versus. PFI) in a more comprehensive way, this meta-analysis was performed.

Methods

To identify relevant studies, Medline, Embase, Cochrane Library, and Scopus database were searched from the inception until October 2014. A meta-analysis was performed using Review Manager 5.2 and STATA 11. Pooled Odds ratio (OR) and/or hazard ratio (HR) with 95% confidence interval (CI) were calculated to examine the risk or hazard association.

Results

A total of 6 studies including 1031 patients qualified for analysis. T3a RCC patients with SFI were significantly associated with poor cancer specific survival(CSS) (HR: 1.47, 95% CI: 1.19–1.83; P<0.001) compared to those with PFI. In T3aNx/N0M0 subgroup, SFI patients also showed a worse prognosis than those with PFI (CSS, HR: 1.94, 95% CI: 1.21–3.12; P = 0.006). T3a RCC patients with SFI had higher Furhman grade, greater possibility of lymph node metastasis, sarcomatoid differentiation and tumour necrosis. Main limitation is the relatively small number of included studies.

Conclusion

The present meta-analysis suggested that SFI is associated with worse CSS in patients with pT3a RCC. However, due to the small number of included studies, future studies with a large sample size are required to further verify our findings.     

Aberrant Functional Connectome in Neurologically Asymptomatic Patients with End-Stage Renal Disease

Purpose

This study aimed to investigate the topological organization of intrinsic functional brain networks in patients with end-stage renal disease (ESRD).

Materials and Methods

Resting-state functional MRI data were collected from 22 patients with ESRD (16 men, 18–61 years) and 29age- and gender-matched healthy controls (HCs, 19 men, 32–61 years). Whole-brain functional networks were obtained by calculating the interregional correlation of low-frequency fluctuations in spontaneous brain activity among 1,024 parcels that cover the entire cerebrum. Weighted graph-based models were then employed to topologically characterize these networks at different global, modular and nodal levels.

Results

Compared to HCs, the patients exhibited significant disruption in parallel information processing over the whole networks (P< 0.05). The disruption was present in all the functional modules (default mode, executive control, sensorimotor and visual networks) although decreased functional connectivity was observed only within the default mode network. Regional analysis showed that the disease disproportionately weakened nodal efficiency of the default mode components and tended to preferentially affect central or hub-like regions. Intriguingly, the network abnormalities correlated with biochemical hemoglobin and serum calcium levels in the patients. Finally, the functional changes were substantively unchanged after correcting for gray matter atrophy in the patients.

Conclusion

Our findings provide evidence for the disconnection nature of ESRD’s brain and therefore have important implications for understanding the neuropathologic substrate of the disease from disrupted network organization perspective.     

The Gap between Estimated Incidence of End-Stage Renal Disease and Use of Therapy

Background

Relatively few data exist on the burden of end-stage renal disease (ESRD) and use of renal replacement therapy (RRT)–a life-saving therapy–in developing regions. No study has quantified the proportion of patients who develop ESRD but are unable to access RRT.

Methods

We performed a comprehensive literature search to estimate use and annual initiation of RRT worldwide, and present these estimates according to World Bank regions. We also present estimates of survival and of etiology of diseases in patients undergoing RRT. Using data on prevalence of diabetes and hypertension, we modeled the incidence of ESRD related to these risk factors in order to quantify the gap between ESRD and use of RRT in developing regions.

Results

We find that 1.9 million patients are undergoing RRT worldwide, with continued use and annual initiation at 316 and 73 per million population respectively. RRT use correlates directly (Pearson’s r = 0.94) with regional income. Hemodialysis remains the dominant form of RRT but there is wide regional variation in its use. With the exception of the Latin American and Caribbean region, it appears that initiation of RRT in developing regions is restricted to fewer than a quarter of patients projected to develop ESRD. This results in at least 1.2 million premature deaths each year due to lack of access to RRT as a result of diabetes and elevated blood pressure and as many as 3.2 million premature deaths due to all causes of ESRD.

Conclusion

Thus, the majority of patients projected to reach ESRD due to diabetes or hypertension in developing regions are unable to access RRT; this gap will increase with rising prevalence of these risk factors worldwide.     

Association of RAC1 Gene Polymorphisms with Primary End-Stage Renal Disease in Chinese Renal Recipients

Background/Objective

RAC1 gene could influence susceptibility to renal failure by altering the activity and expression of Rac1, which is a member of the Rho family of small GTP-binding proteins. In clinical practice, renal transplantation provides the optimal treatment for people with end-stage renal disease (ESRD). The objective of this present study was to determine whether the RAC1 gene polymorphisms were associated with primary ESRD susceptibility in Chinese renal recipients.

Methods

Six single nucleotide polymorphisms (SNPs) of RAC1 gene, including rs836488 T>C, rs702482 A>T, rs10951982 G>A, rs702483 A>G, rs6954996 G>A, and rs9374 G>A, were genotyped in 300 renal transplant recipients (cases) and 998 healthy Chinese subjects (controls) by using TaqMan SNP genotyping assay. Allele, genotype, and haplotype frequencies of the six SNPs were compared between cases and controls. Odds ratios (OR) and 95% confidence intervals (CI) were calculated in logistic regression models to evaluate the associations of the six SNPs with ESRD risk.

Results

The genotype distributions for the six SNPs in controls were consistent with Hardy-Weinberg equilibrium (P > 0.05). Association analysis revealed that three SNPs were significantly associated with ESRD risk. Positive associations with ESRD risk were found for the rs836488, rs702482, and rs702483 in the co-dominant model (minor allele homozygotes versus major allele homozygotes); specifically, the frequencies of the minor allele homozygotes and the minor allele for the three SNPs were higher in the cases than in the controls. In addition, these three SNPs also had associations with increased ESRD risk under the additive model (P < 0.05), and positive associations were also found for the rs836488 in the dominant model (P < 0.05) and for the rs702483 in the recessive model (P < 0.05). All these associations were independent of confounding factors. The other three SNPs (rs10951982, rs6954996, and rs9374), in all comparison models, were not associated with ESRD risk (P > 0.05). In haplotype analysis, carriers with "C-T-G-G-G-G" haplotype had a significantly higher risk of ESRD compared with the most common haplotype "T-A-G-A-G-G" (P = 0.011, OR = 1.46, 95% CI = 1.09–1.94).

Conclusion

This study suggested that polymorphisms of RAC1 gene might influence the susceptibility to ESRD in Chinese Han population. Further studies are necessary to confirm our findings.