Plasma ADMA concentrations associate with aerobic fitness in postmenopausal women

Aims

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide (NO) synthase, an enzyme responsible for the generation of NO. Plasma concentrations of ADMA increase in the elderly and in postmenopausal women. In fact, an elevated ADMA level is a risk factor of cardiovascular disease. Aerobic exercise has a beneficial effect on cardiovascular disease. However, the relationship between ADMA and aerobic fitness is unknown. The aim of this study was to determine whether plasma ADMA concentrations correlate with aerobic fitness levels in postmenopausal women.

Main methods

Thirty healthy postmenopausal women aged 50–76 years participated in this study. We measured plasma concentrations of ADMA and oxygen consumption at the ventilatory threshold (VO_2VT) as an index of aerobic fitness. Subjects were divided into the low aerobic fitness (Low fitness) and high aerobic fitness (High fitness) groups, and the dividing line was set at the median VO_2VT value.

Key findings

VO_2VT was significantly higher in the High fitness group than in the Low fitness group (P < 0.01). The plasma ADMA concentrations in the High fitness group were significantly lower than those in the Low fitness group (P < 0.05). There was a negative correlation between plasma ADMA concentrations and VO_2VT (r = − 0.532, P < 0.01).

Significance

We found that plasma ADMA concentrations were associated with aerobic fitness in postmenopausal women. The results of this study suggest that habitual aerobic exercise may decrease plasma ADMA concentrations.     

Meta-analysis of genetic association of chromosome 9p21 with early-onset coronary artery disease

Purpose

A number of studies reported on associations of single nucleotide polymorphisms (SNPs) present in chromosome 9p21 with early-onset coronary artery disease (CAD). The present study was then undertaken to perform a meta-analysis of all the results published to date.

Methods

All studies of the 9p21 association with early-onset CAD that were published between 2007 and 2012 were retrieved from the PubMed database. RevMan 5.0 software was used to perform meta-analysis of the data that fulfilled the criteria for our meta-analysis. The effect size of four SNPs in the 9p21 region on early-onset CAD risk was assessed based on the odds ratios (ORs) with calculation of 95% confidence interval (CI).

Results

A total of 7123 subjects from 7 case–control studies were genotyped. Meta-analysis demonstrated disease association for rs2383207 (OR = 0.79, 95% CI 0.71–0.88, P < 0.0001), rs2383206 (OR = 1.17, 95% CI 1.10–1.25, P < 0.00001), rs10757278 (OR = 1.28, 95% CI 1.15–1.42, P < 0.00001), and rs10757274 (OR = 1.17, 95% CI 1.08–1.33, P = 0.02).

Conclusion

Genetic variation in the chromosome 9p21 region may contribute to the etiology of early-onset CAD although their effect size is rather small.     

Synergistic effect of anti and pro-inflammatory cytokine genes and their promoter polymorphism with ST-elevation of myocardial infarction

Background

The single-gene approach in association studies of polygenic diseases such as acute myocardial infarction (AMI) is likely to provide limited value. Interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10) plasma levels may be genetically influenced.

Aim

We evaluate the impact of single nucleotide polymorphism of the promoter region of these genes, as well as reciprocal interaction of these genes with ST-elevation of myocardial infarction (STEMI).

Methods

In a case–control study 500 STEMI patients and 500 age- and sex-matched controls were studied. Three single-nucleotide polymorphism genotypes were evaluated by polymerase chain reaction and restriction enzyme analysis and assessed their association with STEMI. The synergistic effects of IL-6, TNF-α and IL-10 gene polymorphisms were evaluated by using logistic regression analysis.

Results

We found that IL-6 and TNF-α concentrations of studied population were significantly different (p < 0.0001) in each genotype of IL-6 − 174G>C and TNF-α − 308G>A gene polymorphisms respectively. A significant association was found in multivariate analysis for the IL-6 − 174G>C [odds ratio (OR): 0.390; 95% confidence interval (CI): 0.176–0.865, p = 0.020] and TNF-α − 308G>A [OR: 0.372; 95% CI: 0.171–808, p = 0.012] gene polymorphisms with STEMI. In contrast, IL-10 − 592C>A gene polymorphism was no longer significant in the multivariate model (OR: 0.678; 95% CI: 0.288 to 1.594, p = 0.373) whereas significant in univariate analysis (OR: 0.697; 95% CI: 0.523–0.929, p = 0.014).

Conclusions

Our findings suggest that IL-6, TNF-α and IL-10 gene polymorphisms all contribute in the association with STEMI whereas the association persisted only for IL-6 and TNF-α but not for IL-10 gene polymorphism with this disease in the multivariate analysis.     

Combined effect between CHRNB3–CHRNA6 region gene variant (rs6474412) and smoking in psoriasis vulgaris severity

Background

Many factors associated with causing psoriasis have been reported, such as the genetic and environmental factors. Smoking is one of the well-established environmental risk factors for psoriasis and also associated with the disease severity. In addition, several studies of psoriasis and psoriatic arthritis have documented gene–environment interactions involving smoking behavior. Although gene polymorphisms on nicotinic acetylcholine receptor subunits CHRNB3–CHRNA6 region gene have been found to correlate with smoking behavior and lung cancer susceptibility in Chinese Han population, the combined effect between the smoking-related genetic variants and smoking behavior on psoriasis vulgaris (PV) has been unreported.

Objective

To evaluate the combined effect of the smoking-related (rs6474412-C/T) polymorphism on CHRNB3–CHRNA6 region gene and smoking behavior on PV risk and clinic traits in Chinese Han population.

Methods

A hospital-based case–control study including 672 subjects (355 PV cases and 317 controls) was conducted. The variant of rs6474412 was typed by SNaPshot Multiplex Kit (Applied Biosystems Co., USA).

Results

The higher body mass index (BMI ≥ 25), smoking behavior and alcohol consumption were risk factors for PV, and the estimated ORs were 1.55 (95% CI, 1.09–2.29), 1.74 (95% CI, 1.22–2.49) and 1.81 (95% CI, 1.25–2.62) respectively. The smoking patients had more severe conditions than non-smokers (OR = 1.71, 95% CI, 1.08–2.70, P = 0.020). The alleles and genotypes of rs6474412 were not associated with risk of PV, but the combined effect of rs6474412 genotype (TT) and smoking behavior increased severity of PV (OR = 5.95; 95% CI, 1.39–25.31; P < 0.05; adjusted OR = 2.20; 95% CI, 1.55–3.14; P < 0.001).

Conclusions

Our results demonstrate that the combined effect of rs6474412-C/T polymorphism in smoking-related CHRNB3–CHRNA6 region gene and smoking behavior may not confer risk to PV, but may have impact on PV severity in Chinese Han population.     

Association study between methylenetetrahydrofolate reductase polymorphisms and unexplained recurrent pregnancy loss: A meta-analysis

Background

Recurrent pregnancy loss is an important clinical problem. Recently, high-level homocysteine in blood has been considered as a possible cause. Genetic polymorphisms in methylenetetrahydrofolate reductase (MTHFR) have been proved to be the common hereditary factors of high-level homocysteine. The association between MTHFR polymorphisms and unexplained recurrent pregnancy loss (URPL) has been reported but with controversial results. The purpose of present study is to collect and analyze published available data, and evaluate the association between MTHFR polymorphisms and URPL.

Methods

A meta-analysis was performed to examine the association between MTHFR polymorphisms (C677T and A1298C) and URPL. Odds ratio (OR) and its 95% confidence interval (CI) were used in each study of genotype and allele contrast.

Result(s)

MTHFR C677T: The analysis included 3559 URPL cases and 5097 healthy controls. Overall random-effects odds ratios (ORs) were 1.68 (95% CI, 1.32–2.13; P < 0.0001) for TT versus total genotypes, 1.35 (95% CI, 1.04–1.76; P = 0.0224) for TT and CT genotype combined versus total genotypes and 1.34 (95%CI, 1.13–1.58; P < 0.0001) for T versus total alleles. Although significant heterogeneity was found in C677T, it became weaker in the East Asian subgroup and the mixed subgroup when separated by ethnic subgroups. The results showed significant association between MTHFR C677T and URPL in the East Asian subgroup (ORs 2.11 for TT versus total genotype (P = 0.0004) and 1.53 for T versus total alleles (P < 0.0001)) and in the mixed subgroup (ORs 3.47 for TT versus total genotypes (P < 0.0001) and 1.80 for T versus total alleles (P < 0.027)), but not in Caucasian subgroup.

MTHFR A1298C

The study involved 1163 URPL cases and 1061 healthy controls. Overall random-effects odds ratios (ORs) were 1.37 (95% CI, 0.71–2.67; P = 0.3456) for CC versus total genotypes, 1.16 (95%CI, 0.98–1.38; P = 0.0833) for CC + AC versus total genotypes and 1.04 (95%CI, 0.84–1.29; P = 0.7112) for C versus total alleles. No significant association between MTHFR A1298C polymorphism and URPL was found.

Conclusions

These results indicate a significant association between MTHFR C677T mutation and URPL in the East Asian subgroup and mixed subgroup, but no significance in MTHFR A1298C mutation.     

Protein tyrosine phosphatase non-receptor type 22 (PTPN22) +1858 C>T gene polymorphism in Egyptian cases with rheumatoid arthritis

Background

Rheumatoid arthritis (RA) is a common autoimmune disease with a complex genetic background. The gene encoding protein tyrosine phosphatase non-receptor type 22 (PTPN22) has been reported to be associated with RA in several populations.

Objectives

This work aimed at assessing the association of PTPN22 +1858 C>T gene polymorphism with the susceptibility, activity and severity of RA in Egyptian subjects.

Subjects and methods

This study included 112 unrelated RA patients who were compared to 122 healthy unrelated individuals taken from the same locality. For all subjects, DNA was genotyped for PTPN22 +1858 C>T (rs2476601) polymorphism using the PCR-RFLP technique. Antibodies to cyclic citrullinated peptides (anti-CCP) were measured by enzyme-linked immunosorbent assay (ELISA).

Results

Cases showed significantly higher PTPN22 +1858 T allele carriage rate (CT + TT genotypes) compared to controls (34.8% vs. 8.2%, OR = 5.98, 95% CI = 2.81–12.73, p < 0.001). Also the frequency of the PTPN22 +1858 T allele was significantly higher among cases compared to controls (18.7% vs. 4.5%, OR = 4.89; 95% CI = 2.45–9.76, p < 0.001). Cases positive to the PTPN22 T allele (CT + TT genotypes) showed no significant difference from those with the CC genotype regarding clinical and immune parameters. Nonetheless, they showed a more functional disability presented in their significantly higher health assessment questionnaire (HAQ) score (p = 0.04).

Conclusions

This study is a confirmatory evidence of the association of the PTPN22 +1858 T allele with susceptibility and functional disability of RA in Egyptian subjects.     

Vitamin D status and vitamin D receptor gene polymorphisms and susceptibility to type 1 diabetes in Egyptian children

Background

Type 1 diabetes mellitus (T1DM) is recognized as a T-cell-mediated autoimmune disease. Vitamin D compounds are known to suppress T-cell activation by binding to vitamin D receptor (VDR); and thus, VDR gene polymorphisms may be related to T-cell-mediated autoimmune diseases. The aim of this study was to investigate the association between vitamin D status and VDR gene polymorphisms and T1DM.

Materials and methods

One hundred and twenty patients with T1DM and one hundred and twenty controls were enrolled in the study. VDR gene BsmI, FokI, ApaI and TaqI polymorphisms were determined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Serum 25-hydroxyvitamin D (25(OH)D) was determined using ELISA.

Result

Serum 25(OH)D levels revealed a vitamin D deficiency or insufficiency in 75% of the patients. The mean levels of vitamin D were significantly lower in patients as compared to their controls (P = < 0.001). VDR BsmI Bb and bb genotypes and VDR FokI Ff and ff genotypes were associated with increased risk of T1DM (OR = 2.3, 95% CI = 1.3–4.2, P = 0.005; OR = 2.2, 95% CI = 1.1–4.7, P = 0.04; OR = 1.8, 95% CI = 1.03–3.04, P = 0.04; OR = 4.03, 95% CI = 1.2–13.1, P = 0.01 respectively), while the VDR ApaI and TaqI polymorphisms were not.

Conclusion

Our study indicated that vitamin D deficiency and VDR BsmI and FokI polymorphisms were associated with T1DM in Egyptian children.     

Associations of the PTEN − 9C>G polymorphism with insulin sensitivity and central obesity in Chinese

Background

Phosphatase and tensin homolog on chromosome 10 gene (PTEN) is known as a tumor-suppressor gene. Previous studies demonstrated that PTEN dysfunction affects the function of insulin. However, investigations of PTEN single nucleotide polymorphisms (SNPs) and IR-related disease associations are limited. The aim of the present study was to investigate whether its polymorphism could be involved in the risk of metabolic syndrome (MetS).

Methods

The genotype frequency of PTEN − 9C>G polymorphism was determined by using a Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) method in 530 subjects with MetS and 202 healthy control subjects of the Han Ethnic Chinese population in a case–control analysis.

Results

The PTEN − 9C>G polymorphism was not associated with MetS or its hyperglycemia, hypertension and hypertriglyceridemia components. In the control individuals aged < 60 years or ≥ 60 years, the CG genotype individuals had lower insulin sensitivity than CC individuals (P < 0.05). In the < 60-year-old MetS group and normal glucose tolerance (NGT) subgroup, the CG individuals had lower insulin sensitivity and higher waist circumference (WC) and waist-height-ratio (WHtR) than CC individuals (P < 0.05). Multiple linear regression analysis showed that the PTEN polymorphism (P = 0.001) contributed independently to 4.2% (adjusted R²) of insulin sensitivity variance (estimated by Matsuda ISI), while age (P = 0.004), gender (P = 0.000) and the PTEN polymorphism (P = 0.032) contributed independently to 5.6% (adjusted R²) of WHtR variance.

Conclusions

The CG genotype of PTEN − 9C>G polymorphism was not associated with MetS and some of its components as well. However, it may not only decrease insulin sensitivity in the healthy control and MetS in pre-elderly or NGT subjects, but may also increase the risk of central obesity among these MetS individuals.     

Polymorphisms of the TLR4 gene and risk of gastric cancer

Objective

Toll-like receptor 4 (TLR4) is an important lipo-polysaccharide (LPS) receptor in gastric epithelial cell signaling transduction and plays critical roles in the development and progression of gastric cancer (GC). We investigated the effects of TLR4 gene polymorphisms and gene–environmental interactions on the risk of GC in Northeastern China.

Methods

We genotyped two single-nucleotide polymorphisms (SNPs) in TLR4 (rs10116253 and rs1927911) in 217 GC patients and 294 cancer-free controls using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Odds ratio (OR) and 95% confidence intervals (CIs) were estimated by unconditional logistic-regression models.

Results

Individuals carrying CC genotype of rs10116253 and TT genotype of rs1927911 had a significantly decreased risk of GC (adjusted OR = 0.33, 95% CI 0.18–0.60, P < 0.001 and adjusted OR = 0.37, 95% CI 0.21–0.67, P = 0.001 respectively), compared with TT genotype of rs10116253 and CC genotype of rs1927911. In addition, the SNP effects were additive to the effects of some known environmental factors without any interaction between them in the susceptibility to GC.

Conclusion

Our data suggested that TLR4 gene polymorphisms may be associated with a decreased risk of GC in Chinese population. And these SNPs and their combined effects with environmental factors may be associated with the risk of GC.     

A common polymorphism in pre-microRNA-146a is associated with lung cancer risk in a Korean population

Introduction

MicroRNAs (miRs) play important roles in the development and progression of human cancers. MiR-146a down-regulates epidermal growth factor receptor and the nuclear factor-κB regulatory kinase interleukin-1 receptor-associated kinase 1 genes that play important roles in lung carcinogenesis. This study was conducted to evaluate the association between rs2910164C>G, a functional polymorphism in the pre-miR-146a, and lung cancer risk.

Material and methods

The rs2910164C>G genotypes were determined in 1094 patients with lung cancer and 1100 healthy controls who were frequency matched for age and gender.

Results

The rs2910164 CG or GG genotype was associated with a significantly decreased risk for lung cancer compared to that of the CC genotype (adjusted odds ratio = 0.80, 95% confidence interval = 0.66–0.96, P = 0.02). When subjects were stratified according to smoking exposure (never, light and heavy smokers), the effect of the rs2910164C>G genotype on lung cancer risk was significant only in never smokers (adjusted odds ratio = 0.66, 95% confidence interval = 0.45–0.96, P = 0.03, under a dominant model for the C allele) and decreased as smoking exposure level increased (P_trend < 0.001). In line with this result, the level of miR-146a expression in the tumor tissues was significantly higher in the GG genotype than in the CC or CG genotype only in never-smokers (P = 0.02).

Conclusions

These findings suggest that the rs2910164C>G in pre-miR-146a may contribute to genetic susceptibility to lung cancer, and that miR-146a might be involved in lung cancer development.     

Association of p53 Arg72Pro polymorphism with bladder cancer: A meta-analysis

Background

p53 tumor suppressor gene Arg72Pro polymorphism has been associated with bladder cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between p53 Arg72Pro polymorphism and bladder cancer.

Methods

Electronic search of PubMed was conducted to select studies. Studies containing available genotype frequencies of Arg72Pro were chosen, and pooled odds ratio (OR) with 95% confidence interval (CI) was used to assess the association.

Results

The final meta-analysis included 14 published studies with 2176 bladder cancer cases and 2798 controls. The results suggested that the variant genotype was associated with the bladder cancer risk (additive model: OR = 1.72, 95% CI: 1.036–1.325, P = 0.011; dominant model: OR = 1.268, 95% CI: 1.003–1.602, P = 0.047) in Asian subgroup. However, the association was not significant between this polymorphism and bladder cancer risk in Caucasian (additive model: OR = 0.773, 95% CI: 0.564–1.059, P = 0.109; dominant model: OR = 0.685, 95% CI: 0.418–1.124, P = 0.134).

Conclusion

This meta-analysis suggests that p53 Arg72Pro polymorphism is associated with increased risk of bladder cancer in Asians. To validate the association between this polymorphism and bladder cancer, further studies with larger participants worldwide are needed.     

Genetic polymorphisms in the DNA repair gene XRCC1 and susceptibility to glioma in a Han population in northeastern China: A case–control study

Background

Several single nucleotide polymorphisms (SNPs) in the X-ray cross-complementing group 1 (XRCC1) gene have been shown to influence DNA repair and to modify cancer susceptibility. To investigate the role of these loci further, we examined the association of three XRCC1 polymorphisms with the risk of gliomas in a Han population in northeastern China.

Methods

Using a PCR–RFLP method, XRCC1 Arg194Trp, Arg280His and Arg399Gln were genotyped in 624 glioma patients and 580 healthy controls.

Results

Significant differences in the distribution of the Arg399Gln allele were detected between glioma patients and healthy controls by a logistic regression analysis (OR = 1.35, 95%CI 1.17–1.68, P = 0.001). Our data also revealed that the Arg399Gln variant (allele A) carriers had an increased glioma risk compared to the wild-type (allele G) homozygous carriers (OR = 1.40, 95%CI 1.12–1.76, P = 0.003).

Conclusions

These results suggest that the XRCC1 Arg399Gln might influence the risk of developing glioma in a Han population in northeastern Chinese.     

Role of EGFR SNPs in survival of advanced lung adenocarcinoma patients treated with Gefitinib

Aim

As a novel molecularly targeting agent for non-small-cell lung cancer (NSCLC), Gefitinib can block its tyrosine kinase activity of the epidermal growth factor receptor (EGFR). Genetic variations in EGFR may affect its protein function or expression and lead to diverse outcomes in NSCLC patients after Gefitinib therapy. Therefore, this prospective study examined whether EGFR single nucleotide polymorphisms (SNPs) are associated with different survival time in advanced lung adenocarcinoma patients treated with Gefitinib.

Methods

One hundred and twenty-eight patients with stage IIIB or IV lung adenocarcinoma receiving Gefitinib target therapy between 2008 and 2010 were recruited in this study. Six EGFR haplotype-tagging SNPs were genotyped by the Sequenom MassArray system. Survival by different genotypes was compared using Kaplan–Meier methods. Cox proportional hazards models were applied to estimate the effect of prognostic factors on overall survival (OS) and progression-free survival (PFS).

Results

After the median 16.6 months of follow-up, the unfavorable EGFR rs2293347AA or GA genotype was significantly correlated with shorter OS (AA vs. GG: 2.0 vs. 21.0 months; hazard ratio (HR) = 2.44, 95% confidence interval (CI) = 1.06–5.56; P = 0.036; GA vs. GG: 15.0 vs. 21.0 months; HR = 1.75, 95%CI = 1.08–2.86, P = 0.025) compared with the favorable rs2293347GG genotype. The prognostic significance of EGFR rs4947492 polymorphism on OS also existed (GG carriers vs. AA carriers: median OS = 24.6 vs. 14.9 months, HR = 0.29, 95%CI = 0.10–0.83, P = 0.021). No significant associations were found among other EGFR SNPs and survival.

Conclusion

EGFR rs2293347 and rs4947492 SNPs might be potential predictive markers of OS in advanced lung adenocarcinoma patients treated with Gefitinib.     

Contribution of PTHrP to mechanical strain-induced fibrochondrogenic differentiation in entheses of Achilles tendon of miniature pigs

Background

Fibrochondrocytes are involved in entheses repair, but their response to mechanical strain (MS) is ill known.

Objective

To determine if parathyroid hormone-related protein (PTHrP) expression in fibrochondrocytes from fibrocartilaginous entheses is modulated by MS, and to further observe the regulatory effects of human (h) PTHrP on fibrochondrocyte differentiation.

Methods

Fibrochondrocytes from fibrocartilaginous entheses of Guizhou miniature pig?s Achilles tendon were submitted or not to MS (4%, 8% or 12% cyclic tensile strain; 1 Hz). Fibrochondrocytes were also exposed to: cyclopamine (Indian hedgehog (Ihh) inhibitor) (10 μM), hPTHrP (10 nM) or cyclopamine/hPTHrP (cyclopamine 10uM+hPTHrP 10 nM). Types I, II and X collagen and PTHrP expressions were measured by real-time RT-PCR and Western blot.

Result

Under 4% strain load for 12 h, types I and II collagen mRNA expressions were increased (+324% and +659%, P<0.001), while type X collagen was decreased (−89%, P<0.001). At 12%, types I and II collagen mRNA expressions were decreased (−62% and −62%, P<0.001), while type X collagen was increased (+375%, P<0.05). Under 4% strain load, PTHrP mRNA expression was increased in relation with strain duration (from 3 to 12 h: +168%, P<0.001), while at 12%, PTHrP expression decreased with time (from 3 to 12 h: −81%, P<0.001). Using cyclopamine for 24 h, PTHrP mRNA expression was significantly decreased (−88%, P<0.05), types I and II collagen were decreased (−90% and −82%, P<0.001), and type X collagen was increased (+261%, P<0.001).

Conclusions

Dynamic MS modulate PTHrP expressions. Thus, PTHrP might play an important role in fibrochondrocyte differentiation, indirectly revealing a role in entheses? formation and repair.     

Apolipoprotein A5 T-1131C variant and risk for metabolic syndrome in obese adolescents

Background

Apolipoprotein A5 (APOA5) gene variants are associated with increased plasma triglycerides, a risk factor for metabolic syndrome (MS). The goal of the current study was the investigation of the distribution of T-1131C variant among obese adolescents with MS compared with healthy controls.

Subjects and methods

The study included 150 obese adolescents (75 males and 75 females) with MS and 204 age and sex matched normal healthy controls (100 males and 104 females). The mean age of the patients was 15.47 ± 2.54 years, ranged from 17 to 20 years. They were genotyped by polymerase chain reaction–restriction fragment length polymorphism for the mutation (T-1131C).

Results

The blood pressure, triglyceride and HOMA-R levels were significantly higher and HDL-C levels were significantly lower in carrier (TC + CC) compared to non-carrier (TT) MS patients. There was accumulation of − 1131C allele frequency in the MS group (31.33% vs. control group 11.76%), p < 0.001. The genotypes were in Hardy–Weinberg equilibrium both in the patients with metabolic syndrome and in the control subjects. Results of analysis of multiple regression models showed that the ApoA5 − 1131C carriers showed an increased incidence of MS (OR = 1.73, 95% CI: 1.41–2.11).

Conclusions

The present study suggests that the 1131T>C polymorphism is a risk factor for the development of metabolic syndrome in obese adolescents.     

The effect of XPD/ERCC2 Lys751Gln polymorphism on acute leukemia risk: A systematic review and meta-analysis

Aims

Epidemiological studies have assessed the association between xeroderma pigmentosum group D (XPD) Lys751Gln and acute leukemia risk with conflicting results. We performed this meta-analysis to derive a more precise estimation of the relationship. Pooled odds ratio (OR) with 95% confidence interval (95% CI) was used to assess the strength of the association.

Results

Ten published case–control studies including a total of 1494 cases and 2259 controls were identified. Overall, significant risk effects of Lys751Gln genotype was found under the dominant model (OR = 1.16; 95% CI = 1.01–1.34; P = 0.032). When stratified by clinical types, the variant genotype was associated with the acute myeloid leukemia (AML) risk under the heterozygote comparison (OR = 1.20; 95% CI = 1.00–1.43; P = 0.048), the homozygote comparison (OR = 1.35; 95% CI = 1.05–1.74; P = 0.019) and the dominant model (OR = 1.23; 95% CI = 1.04–1.45; P = 0.015), respectively. Furthermore, significantly increased risks were also pronounced in Caucasian AML patients (the homozygote comparison: OR = 1.38; 95% CI = 1.07–1.78; P = 0.013; the dominant model: OR = 1.23; 95% CI = 1.03–1.46; P = 0.020; and the recessive model: OR = 1.26; 95% CI = 1.00–1.60; P = 0.050). No evident heterogeneities were observed for the overall data under all genetic models. In addition, no statistical evidence for publication bias was found using the method of Begg's and Egger's tests.

Conclusion

This meta-analysis suggested that XPD Lys751Gln polymorphism might be a risk factor for AML and Caucasian acute leukemia patients.     

Association between resistin + 299A/A genotype and nonalcoholic fatty liver disease in Chinese patients with type 2 diabetes mellitus

Objective

To investigate the relationship between the resistin intronic + 299G/A polymorphism and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM).

Methods

We selected 738 T2DM patients, including 395 with NAFLD and 343 without fatty liver disease, as well as 279 healthy control individuals, and analyzed their resistin + 299G/A polymorphism genotype by polymerase chain reaction–restriction fragment length polymorphism.

Results

Plasma resistin levels in T2DM patients with NAFLD were at the highest (P < 0.05). The frequency of AA genotype at the + 299 site of the resistin gene in patients with concurrent T2DM combined with NAFLD was significantly different from that in the control (P < 0.05). The AA genotype was found to be associated with a 1.80-fold increased risk for T2DM combined with NAFLD, 2.05-fold increased risk for obesity and 2.37-fold increased risk for obesity of abdominal type compared to the GG (P < 0.05, respectively). The multivariate non-conditional logistic regression model analysis further shows that the AA genotype is a risk factor for the development of NAFLD in T2DM patients (OR, 2.32; 95% CI, 1.05–4.68; P < 0.05).

Conclusion

The resistin + 299AA genotype may be associated with increases in the risk of the NAFLD development in T2DM patients.     

The interleukin-4 − 589C/T polymorphism and the risk of asthma: A meta-analysis including 7345 cases and 7819 controls

Background

A number of studies assessed the association of − 589C/T polymorphism in the promoter region of interleukin-4 (IL-4) with asthma in different populations. However, the results were contradictory. A meta-analysis was conducted to investigate the association between polymorphism in the IL-4 and asthma susceptibility.

Methods

Databases including Pubmed, EMBASE, Wanfang Database, China National Knowledge Infrastructure (CNKI) and Weipu Database were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Thirty-four studies involving 7345 cases and 7819 controls were included. Overall, significant association between − 589C/T polymorphism and asthma was observed for TT + CT vs. CC (OR = 1.26; 95% CI 1.12–1.42; P = 0.0001; I² = 26%). In the subgroup analysis by ethnicity, significant associations were found among Asians (OR = 1.36; 95% CI 1.07–1.73; P = 0.01; I² = 0%) and Caucasians (OR = 1.30; 95% CI 1.09–1.54; P = 0.004; I² = 53%) but not among African Americans (OR = 1.20; 95% CI 0.72–2.00; P = 0.48; I² = 48%). In the subgroup analysis by atopic status, no significant association was found among atopic asthma patients (OR = 1.20; 95% CI 0.92–1.34; P = 0.27; I² = 6%) and non-atopic asthma patients (OR = 0.97; 95% CI 0.73–1.28; P = 0.81; I² = 0%).

Conclusions

This meta-analysis suggested that the IL-4 − 589C/T polymorphism was a risk factor of asthma.     

Population-based and family-based studies on the protein tyrosine phosphatase non-receptor 22 gene polymorphism and type 1 diabetes: A meta-analysis

Purpose

Studies investigating the association between PTPN22 gene C1858T polymorphism and type 1 diabetes (T1D) susceptibility among Caucasian population have reported conflicting results. To investigate this inconsistency, we performed a meta-analysis of all available studies dealing with the relationship between the PTPN22 C1858T polymorphism and T1D.

Methods

Databases including PubMed, Web of Science, and EMBASE were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association.

Results

In total, 33 population-based studies with 22, 485 cases and 35, 292 controls, 9 family-based studies involving 7276 families were included. Under the random-effects model, the per-allele overall OR of the C1858T polymorphism for T1D was 1.89 (95% CI: 1.76–2.02, P < 10^− 5) by pooling all available case–control studies. In addition, we found significant evidence for overtransmission of the risk T allele in family-based studies (overall OR _TDT = 1.58, 95% CI: 1.43–1.74; P < 10^− 5). The summary OR from case–control and family-based association studies was 1.81 (95% CI: 1.70–1.93, P < 10^− 5).

Conclusions

In conclusion, this meta-analysis suggests that C1858T polymorphism in PTPN22 is associated with elevated T1D risk among Caucasian population.     

Interleukin-23 receptor genetic variants contribute to susceptibility of multiple cancers

Aim

Interleukin-23 (IL-23) and IL-23 receptor (IL23R) play an important role during the T-helper 17 (Th17) cell-mediated inflammatory process as well as pathogenesis of multiple cancers. Several IL-23R single nucleotide polymorphisms (SNPs), especially rs6682925, rs10889677 and rs1884444 polymorphisms, are considered to have significant impacts on susceptibility of multiple cancers. A number of case-control studies have explored the role these genetic polymorphisms in development of carcinogenesis, but the conclusions are inconsistent. Therefore, we conducted this meta-analysis to systematically investigate the associations between the three genetic variants and multiple cancer risk.

Methods

A total of ten studies are eligible (12,211 patients and 14,650 controls). Pooled odds ratios (ORs) and the 95% confidence interval (95% CI) were appropriately calculated using either fixed-effect model or random-effect model.

Results

Significant associations between rs6682925 or rs10889677 polymorphism and cancer risk were found (OR = 1.11, 95% CI = 1.03–1.21, P = 0.007; or OR = 0.85, 95% CI = 0.71–0.92, P = 0.001). However, there was no such association between rs1884444 genotypes and cancer susceptibility (P > 0.05).

Conclusion

These findings reveal that the IL-23R rs6682925 and rs10889677 genetic variants play a more important part in pathogenesis of multiple cancers.