Common polymorphisms (rs2241766 and rs1501299) in the ADIPOQ gene are not associated with hypertension susceptibility among the Chinese

The ADIPOQ gene has been implicated in the etiology of hypertension. However, the results have been inconsistent. In this study, a meta-analysis was performed to assess the associations of ADIPOQ polymorphisms with hypertension risk among the Chinese. Published literature from PubMed, CNKI and Wanfang Data were retrieved. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using fixed- or random-effects model. Six studies (1,812 cases and 2,631 controls) for rs2241766 polymorphism and four studies (1,449 cases and 2,175 controls) for rs1501299 polymorphism were identified. A marginally significant association was observed for rs2241766 polymorphism under recessive genetic model (GG vs. GT+TT: OR = 1.22, 95 % CI 1.01-1.48) and for rs1501299 polymorphism under heterogeneous co-dominant model (TG vs. GG: OR = 0.86, 95 % CI 0.75-0.99) and dominant model (TT+TG vs. GG: OR = 0.85, 95 % CI 0.74-0.98). In addition, under other genetic models, there was no significant association for rs2241766 polymorphism (GG vs. TT: OR = 1.20, 95 % CI 0.98-1.48; GT vs. TT: OR = 0.97, 95 % CI 0.85-1.10; GG+GT vs. TT: OR = 1.01, 95 % CI 0.90-1.15) and for rs1501299 polymorphism (TT vs. GG: OR = 0.82, 95 % CI 0.62-1.08; TT vs. TG+GG: OR = 0.87, 95 % CI 0.66-1.14). However, the associations above were not robust by sensitivity analysis. The present meta-analysis indicated the limited evidence of the significant associations between ADIPOQ gene polymorphisms and hypertension susceptibility among the Chinese.     

MTHFR polymorphisms and ovarian cancer risk: a meta-analysis

The C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) have been reported to alter the risk of ovarian cancer. However, the results are still inconclusive. For better understanding of the effect of these two polymorphisms on ovarian cancer risk, a meta-analysis was performed. An extensive search was performed to identify all case–control studies investigating such association. The strength of association between these two polymorphisms and ovarian cancer risk was assessed by odds ratio (OR) with the corresponding 95?% confidence interval (95?% CI). 3,496 cases and 3,631 controls for C677T polymorphism and 3,280 cases and 3,346 controls for A1298C polymorphism were included in this meta-analysis. The results suggested that there were no significant associations between C677T and A1298C polymorphisms and ovarian cancer risk in overall comparisons in all genetic models (For C677T: TT vs. CC: OR?=?0.94, 95?% CI?=?0.71–1.24, P?=?0.65; CT vs. CC: OR?=?1.03, 95?% CI?=?0.93–1.14, P?=?0.57; TT/CT vs. CC: OR?=?1.01, 95?% CI?=?0.88–1.16, P?=?0.87; TT vs. CC/CT: OR?=?0.93, 95?% CI?=?0.72–1.20, P?=?0.58. For A1298C: CC vs. AA: OR?=?1.05, 95?% CI?=?0.88–1.25, P?=?0.65; CA vs. AA: OR?=?0.98, 95?% CI?=?0.88–1.08, P?=?0.66; CC/CA vs. AA: OR?=?0.99, 95?% CI?=?0.90–1.09, P?=?0.85; CC vs. AA/CA: OR?=?1.06, 95?% CI?=?0.90–1.26, P?=?0.46). Subgroup analysis based on ethnicities and influence analysis did not perturb the results. In conclusion, the results of this meta-analysis indicate that the MTHFR C677T and A1298C polymorphisms are not associated with ovarian cancer risk, especially in Caucasians.     

Association between single-nucleotide polymorphisms in pre-miRNAs and the risk of asthma in a Chinese population

Single-nucleotide polymorphisms (SNPs) in pre-miRNAs may alter microRNA (miRNA) expression levels or processing and contribute to susceptibility to a wide range of diseases. We investigated the correlation between four SNPs (rs11614913, rs3746444, rs2910164, and rs229283) in pre-miRNAs and the risk of asthma in 220 asthma patients and 540 controls using polymerase chain reaction-restriction fragment length polymorphism methodology and DNA-sequencing. There were significant differences in the genotype and allelic distribution of rs2910164G/C and rs2292832C/T polymorphisms among cases and controls. The CC genotype and C allele of rs2910164G/C were significantly associated with a decreased risk of asthma (CC vs. GG, odds ratio [OR]?= 0.51, 95% confidence interval [CI]: 0.31-0.82; C vs. G, OR = 0.74, 95% CI: 0.59-0.93). Similarly, the TT genotype and T allele of rs2292832C/T were significantly associated with a decreased risk of asthma (TT vs. CC, OR = 0.56, 95% CI: 0.33-0.95; T vs. C, OR = 0.71, 95% CI: 0.53-0.95). However, no significant association between the other two polymorphisms (i.e., rs11614913C/T and rs3746444C/T) and the risk of asthma was observed. Our data indicate that rs2910164G/C and rs2292832C/T may play a role in the development of asthma.     

MDM2 SNP309 is associated with endometrial cancer susceptibility: a meta-analysis

Epidemiological studies have investigated the association between MDM2 promoter SNP 309 (T/G) and endometrial cancer susceptibility. However, the results are still controversial. To obtain a more precise estimate of the relationship, we conducted a meta-analysis of 1,001 cases and 1,889 controls from 6 published case-control studies (one of five articles contains two studies) to estimate the effect of SNP309 on endometrial cancer risk. The strength of association between MDM2 SNP309 and endometrial cancer susceptibility was assessed by calculating pooled odds ratios (ORs) with 95% confidence intervals (CIs). When all the eligible studies were pooled in the meta-analysis, we found that elevated endometrial cancer risk was significantly associated with GG variant genotype, however, heterozygous genotype TG seemed to be only a minor modifier on endometrial cancer risk (for GG vs. TT, OR?=?1.54, 95% CI?=?1.21-1.95, P?=?0.0004; for TG vs. TT, OR?=?0.96, 95% CI?=?0.81-1.14, P?=?0.66; for dominant model, OR?=?1.09, 95% CI?=?0.93-1.29, P?=?0.29; for recessive model, OR?=?1.65, 95% CI?=?1.33-2.04, P?相似文献   

Long non-coding RNA POLR2E gene polymorphisms increased the risk of prostate cancer in a sample of the Iranian population

The current study aimed to examine the impact of POLR2E rs1046040 and rs3787016 polymorphisms on prostate cancer (PCa) risk in a sample of southeast Iranian population. The present case-control study was performed on 178 patients with PCa and 180 benign prostatic hyperplasia (BPH). Genotyping of the variants was done by mismatch PCR-RFLP. The findings showed that the rs3787016 C?>?T variant significantly increased the risk of PCa in codominant (OR?=?1.84, 95% CI?=?1.12-3.03, P?=?0.018, CT vs CC), dominant (OR?=?1.88, 95% CI?=?1.63-3.05, P?=?0.011, CT?+?TT vas CC) and allele (OR?=?1.77, 95% CI?=?1.52-2.72, P?=?0.010, T vs C) inheritance model. Regarding rs1046040 C?>?T polymorphism, the findings revealed that the CT genotype significantly increased the risk of PCa compared to the CC genotype (OR?=?1.60, 95% CI?=?1.03-2.49, P?=?0.043). Furthermore, rs3787016 CT/rs1046040?CC as well as rs3787016 CT/rs1046040 CT increased the risk of PCa compared to the CC/CC genotype (p?=?0.029 and p?=?0.014, respectively). Haplotype analysis proposed that rs3787016 T/rs1046040 C significantly increased the risk of PCa compared to C/C (p?=?0.037). No significant association was observed between POLR2E variants and clinicopathological characteristics of PCa patients. In conclusion, the findings propose that POLR2E variants may be a risk factor for susceptibility to PCa in a sample of Iranian population.     

Association of excision repair cross-complimentary group 1 gene polymorphisms with breast and ovarian cancer susceptibility

The role of excision repair cross-complimentary group 1 (ERCC1) gene polymorphisms in breast and ovarian cancer development has long been controversial and existing data were inconsistent. Here, we conducted a comprehensive meta-analysis to better clarify the association. Case-control studies published from December 2008 to November 2018 were assessed. The statistical analyses of the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (CIs) were calculated. Fifteen articles with 24 case-control studies and 3 ERCC1 polymorphisms were enrolled. A total of 20 923 participants including 9896 cases and 11 027 controls were analyzed. The results showed that C to T variation in the ERCC1 rs11615 (C/T) polymorphisms was correlated with breast cancer susceptibility (T vs C: OR = 1.19, 95% CI = 1.02-1.38; TT + CT vs CC: OR = 1.24, 95% CI = 1.12-1.36). ERCC1 rs3212986 (C/A) polymorphisms posed an increased risk for breast and ovarian cancer as whole (A vs C: OR = 1.12, 95% CI = 1.01-1.25; AA + CA vs CC: OR = 1.11, 95% CI = 1.02-1.22), and presented especially higher risk for ovarian cancer (A vs C: OR = 1.31, 95% CI = 1.05-1.63; AA vs CA + CC: OR = 1.66, 95% CI = 1.12-2.47; AA vs CC: OR = 1.72, 95% CI = 1.12-2.64). Meanwhile, neither overall group analyses nor stratified analyses displayed any association of ERCC1 rs2298881 (A/C) polymorphisms in breast and ovarian cancer susceptibility. This meta-analysis suggested that ERCC1 rs11615 (C/T) polymorphisms were associated with breast cancer susceptibility and rs3212986 (C/A) polymorphisms were especially correlated with ovarian cancer risk. More case-control studies with well-adjusted data and diverse populations are essential for validation of our conclusion.     

miR-499 rs3746444 polymorphism is associated with cancer development among Asians and related to breast cancer susceptibility

To derive a more precise estimation of the relationship between miR-499 rs3746444 polymorphism (A>G) and cancer risk, a meta-analysis was performed. A total of 9 studies including 6,077 cases and 7,199 controls were involved in this meta-analysis. Overall, no significantly elevated cancer risk was associated with miR-499 G allele when all studies were pooled into the meta-analysis (AG vs. AA: OR?=?1.14, 95?% CI?=?0.98–1.32; GG vs. AA: OR?=?1.12, 95?% CI?=?0.95–1.33; dominant model: OR?=?1.13, 95?% CI?=?0.99–1.29; recessive model: OR?=?1.05, 95?% CI?=?0.83–1.33). In the subgroup analysis by ethnicity, significantly increased risk was only found for Asians (dominant model: OR?=?1.22, 95?% CI?=?1.02–1.46). When stratified by study design, no statistically significantly elevated risks were found in hospital-based studies or population-based studies. In the subgroup analysis by cancer type, significant cancer risk change was only found for breast cancer when miR-499 G allele was included (dominant model: OR?=?1.13, 95?% CI?=?1.01–1.26). In conclusion, this meta-analysis suggests that the miR-499 rs3746444 polymorphism (A>G) is a low-penetrant risk factor for cancer development among Asians and may contribute to breast cancer susceptibility.     

Toll-like receptor 4 Asp299Gly and Thr399Ile polymorphisms in cancer: a meta-analysis

Toll-like receptor 4 (TLR4) is critical in the recognition of Gram-negative bacteria serving as a key immune system effector. Recently, a number of case-control studies were conducted to investigate the association between TLR4 gene polymorphism and cancer risk, especially Asp299Gly and Thr399Ile polymorphisms. However, published data were still conflicting. In this paper, we summarized 9463 cancer cases and 10,825 controls from 22 studies and attempted to assess the susceptibility of TLR4 gene polymorphism to cancers by a synthetical meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the relationship. Our results suggested that Asp299Gly represented a risk factor on cancers in digestive system (G allele versus A allele, OR=1.64, 95% CI: 1.02-2.64; GA+GG versus AA, OR=1.64, 95% CI: 1.00-2.71) but tend to have a protective effect on prostate cancer (GG versus AA, OR=0.37, 95% CI: 0.14-0.98; GG versus GA+AA, OR=0.37, 95% CI: 0.14-0.98). Thr399Ile polymorphism was significantly associated with an elevated cancer risk in overall analysis (T allele versus C allele, OR=1.72, 95% CI: 1.27-2.33; TC versus CC, OR=1.63, 95% CI: 1.18-2.26; TT+TC versus CC, OR=1.70, 95% CI: 1.24-2.34) and especially in gastrointestinal subgroup (T allele versus C allele, OR=2.01, 95% CI: 1.40-2.89; TC versus CC, OR=1.86, 95% CI: 1.26-2.74; TT+TC versus CC, OR=1.97, 95% CI: 1.35-2.88). Further prospective researches with larger numbers of worldwide participants are warranted to draw comprehensive and true conclusions.     

Genetic association between IL-27 rs153109 polymorphism and cancer risk in Chinese population: a meta-analysis

IL-27 plays an important role in anti-cancer activity. The -964A/G polymorphism in IL-27 gene has been implicated in susceptibility to cancer, but the results were conflicting. The aim of this study was to assess the association between this polymorphism and cancer risk. Pubmed and Wanfang database were searched for all publications concerning IL-27 -964A/G polymorphism and cancer risk. Odds ratio (OR) and 95% confidence interval (CI) were used to assess the strength of association. Statistical analysis was performed using Stata 11.0 software. A total of eight case–control studies including 2044 cancer cases and 2197 controls were identified. Overall, significant association between IL-27 -964A/G polymorphism and cancer risk was observed (GG versus AA: OR?=?1.26, 95% CI?=?1.03–1.52; GG versus AG?+?AA: OR?=?1.20, 95% CI?=?1.00–1.44). In subgroup analysis based on cancer type, significant association was found in colorectal cancer (GG versus AA: OR?=?1.55, 95% CI?=?1.07–2.27; AG versus AA: OR?=?1.31, 95% CI?=?1.02–1.67). The current meta-analysis suggests that IL-27 -964A/G polymorphism might enhance cancer risk. However, large-scale and well-designed studies are still needed to confirm the result of our meta-analysis. The association of IL-27 polymorphism with colorectal cancer may provide insight for future therapies.     

Meta-analysis of vitamin D receptor gene polymorphisms and benign prostatic hyperplasia risk

The association between vitamin D receptor (VDR) gene polymorphisms and risk of benign prostatic hyperplasia (BPH) has been investigated in numerous publications, but published results remain inconclusive. Hence, we conducted this meta-analysis to derive a more precise conclusion. Four polymorphisms (Taq-I, Bsm-I, Apa-I, and Fok-I) of the VDR gene with risk of BPH from six case–control studies and one cohort study involving 2,248 individuals were identified from PubMed and China National Knowledge Internet databases up to November 20, 2013 (updated on March 5, 2014). After data extraction, the meta-analysis was performed using Comprehensive Meta-Analysis software. All four VDR polymorphisms were not associated with the risk of BPH [Taq-I: OR 0.61, 95 % CI (0.38–1.24) for tt vs. TT; Bsm-I: OR 1.27, 95 % CI (0.96–1.69) for bb vs. BB; Apa-I: OR 1.26, 95 % CI (0.64–2.46) for aa vs. AA; Fok-I: OR 0.95, 95 % CI (0.60–1.50) for ff vs. FF]. Subgroup analysis according to ethnicity for Taq-I polymorphism also showed that the polymorphism was not associated with risk of BPH for either Caucasians [OR 0.74, 95 % CI (0.31–1.78) for tt vs. TT] or Asians [OR 0.35, 95 % CI (0.11–1.11) for tt vs. TT]. However, results of this meta-analysis should be treated with caution because this meta-analysis has several limitations. We propose to conduct a high-quality study with large sample size to further identify the association between VDR gene polymorphisms and BPH susceptibility.     

Interleukin-12B rs3212227 polymorphism and cancer risk: a meta-analysis

IL-12 plays a very important role in the development and progress of cancer. IL-12B rs3212227 polymorphism has been reported and many studies have focused on the role of this polymorphism in various cancers. However, the association between IL-12B rs3212227 polymorphism and cancer risk remains controversial. Therefore, we performed a systematic meta-analysis to estimate the overall cancer risk associated with this gene polymorphism and to quantify any potential between-study heterogeneity. PubMed and Embase databases were searched for case–control studies published up to April 1, 2012 that investigated IL-12B rs3212227 polymorphism and cancer risk. Odds ratios (OR) with 95?% confidence intervals (95?% CI) were used to access the strength of this association. Heterogeneity among articles and publication bias were also verified. Ten studies with 2,954 cancer patients and 3,276 healthy controls were included. This meta-analysis showed that there was a significant association between IL-12B rs3212227 polymorphism and overall cancer risk (CC/AC vs AA: OR?=?1.32, 95?% CI?=?1.06–1.63). When stratified by cancer type, we found a significant increased risk in cervical and nasopharyngeal cancer (OR?=?1.34, 95?% CI?=?1.04–1.73; OR?=?2.03, 95?% CI?=?1.57–2.63, respectively). In the stratified analysis, we also observed a similar association in population-based studies (OR?=?1.34, 95?% CI?=?1.00–1.80), Asian populations (OR?=?1.33, 95 % CI?=?1.06–1.67) and European populations (OR?=?1.54, 95 % CI?=?1.04–2.28). According to the results of our meta-analysis, IL-12B rs3212227 polymorphism probably is associated with a high risk of cancer.     

miR-196a2 C allele is a low-penetrant risk factor for cancer development

Published data on the association between miR-196a2 T/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 21 studies including 10,441 cases and 12,353 controls were involved in this meta-analysis. Overall, significantly elevated cancer risk was associated with miR-196a2 C allele when all studies were pooled into the meta-analysis (TC vs. TT: OR=1.23, 95% CI=1.11-1.36; CC vs. TT: OR=1.30, 95% CI=1.14-1.48; dominant model: OR=1.25, 95% CI=1.13-1.38). In the subgroup analysis by ethnicity, significantly increased risks were found in Asains (TC vs. TT: OR=1.24, 95% CI=1.10-1.40; CC vs. TT: OR=1.31, 95% CI=1.13-1.52; dominant model: OR=1.26, 95% CI=1.12-1.41) but with bordline statistical significance in Caucasians (TC vs. TT: OR=1.15, 95% CI=1.00-1.31). In the subgroup analysis by cancer type, statistically significantly increased risks were found for breast cancer (TC vs. TT: OR=1.15, 95% CI=1.01-1.31; CC vs. TT: OR=1.30, 95% CI=1.01-1.68; dominant model: OR=1.22, 95% CI=1.00-1.50; and recessive model: OR=1.11, 95% CI=1.01-1.23) and lung cancer (CC vs. TT: OR=1.30, 95% CI=1.10-1.54; and recessive model: OR=1.18, 95% CI=1.02-1.36). When stratified by study design, statistically significantly elevated risk was found in hospital-based studies (TC vs. TT: OR=1.30, 95% CI=1.13-1.49; CC vs. TT: OR=1.37, 95% CI=1.14-1.66; dominant model: OR=1.32, 95% CI=1.15-1.53) and population-based studies (CC vs. TT: OR=1.19, 95% CI=1.06-1.35; dominant model: OR=1.13, 95% CI=1.01-1.25). Despite some limitations, this meta-analysis suggests that the miR-196a2 C allele is a low-penetrant risk factor for cancer development.     

The ?159C/T polymorphism in the CD14 gene and the risk of asthma: a meta-analysis

The -159C/T polymorphism in the CD14 gene has been implicated in susceptibility to asthma, but a large number of studies have reported inconclusive results. The aim of this study is to investigate the association between the -159C/T polymorphism in the CD14 gene and the risk of asthma by meta-analysis. We searched Pubmed, Embase, CNKI database, Wanfang database, Weipu database, and Chinese Biomedical database, covering all publications (last search been performed on April 20, 2010). Statistical analysis was performed by using the softwares Revman 4.2 and STATA 10.0. A total of 17 case-control studies in 17 articles (4,246 cases and 3,631 controls) were included in this meta-analysis. There was no association between this polymorphism and asthma risk in combined analyses (odds ratio (OR)?=?0.86 and 95% confidence interval (95% CI)?=?0.72-1.02, P?=?0.09 for TC?+?TT vs. CC). In the subgroup analysis by age, ethnicity, and atopic status, no significant associations of asthma risks were obtained from age groups, ethnic groups, and atopic groups for TC?+?TT vs. CC comparison. For atopic population, significant decreased atopic asthma risks were found among Asian population (OR?=?0.69, 95% CI 0.52-0.92, P?=?0.01) and children population (OR?=?0.69, 95% CI 0.54-0.89, P?=?0.0004) for TC?+?TT vs. CC comparison. This meta-analysis suggests that CD14 is a candidate gene for atopic asthma susceptibility. The -159C/T polymorphism may be a protective factor for atopic asthma in Asian and children. More studies are needed to validate these associations.     

Association between ATM polymorphisms and cancer risk: a meta-analysis

To date, epidemiological studies have assessed the association between Ataxia-telangiectasia mutated (ATM) gene polymorphisms and cancer risk, including lung cancer, breast cancer, glioma and pancreatic cancer. However, the results of these studies remain controversial. We aimed to examine the associations between two SNPs (rs664143 and rs664677) and cancer risk by conducting a meta-analysis of case–control studies. A total of 12 publications were included in this meta-analysis, 8 for rs664143 and 7 for rs664677. Overall, rs664143 heterozygote carriers turned out to be associated with cancer risk (OR = 1.18, 95% CI 1.02–1.36). In the subgroup analysis by cancer type, we observed that the ATM rs664143 polymorphism was significantly associated with lung cancer risk (GA vs. GG: OR = 1.48, 95% CI 1.18–1.85, AA vs. GG: OR = 1.51, 95% CI 1.18–1.93) and rs664677 polymorphism was associated with decreased lung cancr risk and increased breast cancer risk (for lung cancer: TC vs. TT: OR = 0.76, 95% CI 0.62–0.92, CC vs. TT: OR = 0.80, 95% CI 0.64–0.99 and for breast cancer: TC vs. TT: OR = 1.42, 95% CI 1.17–1.73, CC vs. TT: OR = 1.51, 95% CI 1.21–1.87). In the subgroup analysis by region, we also observed that individuals with ATM rs664143 GA or AA genotype had an obvious increased cancer risk among Asian people (GA vs. GG: OR = 1.40, 95% CI 1.20–1.63, AA vs. GG: OR = 1.37, 95% CI 1.16–1.62). In conclusion, ATM rs664143 polymorphism was associated with cancer susceptibility. ATM rs664143 polymorphism was significantly associated with lung cancer risk. ATM rs664677 polymorphism was associated with decreased lung cancer risk as well as increased breast cancer risk.     

MTHFR C677T polymorphism contributes to colorectal cancer susceptibility: evidence from 61 case–control studies

Methylenetetrahydrofolate reductase (MTHFR) is believed to be involved in folate metabolism which plays a critical role in carcinogenesis. To date, many case-control studies have investigated the association between MTHFR C677T polymorphism and colorectal cancer risk. However, the results were inconsistent. In order to derive a more precise estimation of the association, we conducted this meta-analysis. This meta-analysis recruited 61 published studies which were selected by a search of PubMed up to 31st September 2011, including 16,111 colorectal cancer cases and 23,192 controls. We used crude odds ratios (ORs) with 95?% confidence intervals (CIs) to assess the association between MTHFR C677T polymorphism and colorectal cancer susceptibility. Our results showed that MTHFR C667T polymorphism contributed to the decreased colorectal cancer risk in overall population (for TT vs. CC: OR?=?0.89, 95?% CI?=?0.82-0.97; for TT vs. CT/CC: OR?=?0.88, 95?% CI?=?0.83-0.92). In subgroup analysis by ethnicity, the results also indicated a correlation between the T allele of MTHFR C667T and the colorectal cancer risk in Asian population (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.69-0.97; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.74-0.90). Additionally, the correlation was also observed in male subgroup in sub-analysis by gender (for TT vs. CC: OR?=?0.82, 95?% CI?=?0.71-0.93; for TT vs. CT/CC: OR?=?0.81, 95?% CI?=?0.71-0.92). In summary, our meta-analysis strongly indicated the MTHFR C667T polymorphism was associated with a reduced risk of CRC.     

Polymorphisms in the cytotoxic T-lymphocyte antigen 4 gene and acute rejection risk in transplant recipients

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) gene polymorphisms have been reported to influence the risk for acute rejection (AR) in transplant recipients. However, the results still remain controversial and ambiguous. The objective of the current study was to conduct a meta-analysis investigating the association between polymorphisms in the CTLA-4 gene and the risk of AR in transplant recipients. Electronic searches for all publications were conducted on associations between this variant and acute rejection in Medline and Embase databases through November 2011. Crude odds ratios (ORs) with 95 % confidence intervals (CIs) were calculated to estimate the strength of the association. Three polymorphisms (+49 adenine/guanine [+49A/G], -318 cytosine/thymine [-318C/T], and the +6230G/A polymorphism [CT60]) in 18 case-control studies from ten articles were analyzed. This meta-analysis included 2,081 cases of transplant recipients in which 813 cases developed AR and 1,268 cases did not develop AR. The results indicated that there was no statistically significant association between the risk of AR and the +49A/G polymorphism or the -318C/T polymorphism (+49A/G: OR = 0.876, 95 % CI = 0.650-1.180 for GG vs. AA; OR = 1.121, 95 % CI = 0.911-1.379 for AG + GG vs. AA; -318C/T: OR = 0.397, 95 % CI = 0.138-1.143 for TT vs. CC; OR = 0.987, 95 %CI = 0.553-1.760 for CT + TT vs. CC). However, individuals who carried CT60 A allele might have a decreased risk of AR (AA vs. GG OR = 0.535, 95 % CI = 0.340-0.841, A vs. G OR = 0.759, 95 % CI = 0.612-0.914) in liver transplant recipients among Europeans, but because only two studies were included, so the result should be caution. In further stratified analyses for the +49A/G and the -318C/T polymorphisms, no obvious significant associations were found in subgroups of renal transplant recipients and Europeans, a reduced incidence of acute rejection was observed in liver transplant recipients that are homogenous for +49G (OR = 0.638, 95 % CI = 0.427-0.954 for GG vs. AA/AG), while this has not been observed in renal transplant recipients. Overall this meta-analysis suggests that +49A/G and the -318C/T polymorphisms in CTLA-4 may be not associated with the risk of rejection after organ transplantation, but CTLA +49A/G and +6230G/A polymorphisms may be associated with acute rejection after liver transplantation, not after renal transplantation. In future, more studies should be included to evaluate the association between +6230G/A polymorphism and AR risk.     

Two Novel Susceptibility SNPs for Ischemic Stroke Using Exome Sequencing in Chinese Han Population

Genome-wide association studies (GWAS) of ischemic stroke (IS) have been performed on several cohorts of Caucasian or African population and Japanese, resulting in somewhat inconsistent conclusion. We aimed to identify susceptibility loci for IS by exome sequencing in a Chinese Han population. Exome sequencing was used to screen susceptibility loci among 100 cases and 100 matched controls. Significant SNPs from the first stage were verified in up to 3,554 participants from three hospital-based case–control studies. In the initial exome sequencing analysis, rs10489177 in c1orf156 gene located on chromosome 1q24 (p?<?1?×?10^?8) and rs17118 in XYLB gene located on chromosome 3p21 (p?<?1?×?10^?6) were found to be significantly associated with IS. In the following validation stage, significantly increased odds ratios were observed in individuals with rs10489177 GG (OR?=?2.02, 95 % CI?=?1.35–3.03) or rs17118 AA genotype (OR?=?1.50, 95 % CI?=?1.17–1.91). The rs10489177 GG genotype was associated with significantly increased risk for IS in individuals without hypertension (OR?=?2.78, 95 % CI?=?1.59–4.86) and in individuals without diabetes (OR?=?1.93, 95 % CI?=?1.27–2.94). In contrast, the rs17118 AA genotype may significantly increase the risk for IS, particularly for individuals with hypertension (OR?=?1.73, 95 % CI?=?1.08–2.78) and for individuals without diabetes (OR?=?1.52, 95 % CI?=?1.17–1.98) or non-smoker (OR?=?1.59, 95 % CI?=?1.16–2.19). Collectively, our study identified two novel loci (rs17118 and rs10489177) which were associated with an increased risk for IS in Chinese Han populations. Further studies are needed to confirm these associations in other populations and elucidate the biological mechanisms underlying the observed associations.