MiRNA-146a的单核苷酸多态性rs2910164与2型糖尿病相关性的系统分析

目的 对miR-146a rs2910164 与T2DM相关性进行荟萃分析.方法 在Pubmed、EMBASE、以及CNKI、万方数据库进行文献检索,收集病例对照研究,对纳入的文献进行质量评价,并获取相关数据,使用Stata12进行meta分析.结果共检索文献499篇,最终有4篇符合入选标准,其中病例组共2069人,对照组1950人.结果显示rs2910164的基因位点及各遗传模型与T2DM均无明显相关性,但以种族进行分层分析,在各遗传模型中纯合子模型及隐性模型提示与白种人T2DM有关,增加T2DM的发病风险(OR=1.79 95% CI 1.07~3.00, PH=0.216;GG+GC/CC:OR=1.80 95% CI 1.09~2.97, PH=0.314).在敏感性分析中去除Wang等人的研究,此基因位点及纯合子模型与T2DM有关,也提示增加T2DM的发病风险(G/C:OR=1.32 95% CI 1.05~1.67, PH =0.104;GG/CC:OR=1.97 95% CI 1.49~2.61, PH=0.420).结论 miR-146a rs2910164可能增加T2DM的患病风险,但仍需纳入更多高质量、更多不同种族的文献研究,进行综合分析.     

Association between miRNA-146a rs2910164 (G/C) polymorphism with the susceptibility to chronic HBV infection and spontaneous viral clearance in an Iranian population

Hepatitis B virus (HBV) infection is one of the clinical dilemmas in chronic liver diseases. MicroRNAs (miRNAs) are small noncoding RNA molecules that play an important role in the pathogenesis of liver diseases and single nucleotide polymorphisms (SNPs) in miRNA genes affect the clinical course of HBV infection. Previous studies have shown that miRNA-146a rs2910164 polymorphism can be associated with the pathogenesis of liver diseases such as hepatocellular carcinoma. The present study investigated the association between miRNA-146a rs2910164 polymorphism and susceptibility to HBV infection in an Iranian population. The study comprised 266 patients with chronic HBV infection, 172 patients with spontaneous viral clearance (SVC) after acute HBV infection, and 266 healthy control adjusted for sex and age. The genotyping of the miRNA-146a rs2910164 polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Our data revealed that GG genotype and G allele of miRNA-146a rs2910164 SNP is dominated (P < 0.001) in patients with chronic HBV infection (Odds ratio [OR] = 3.92; 95% confidence interval [CI] = 2.1-7.32). miRNA-146a rs2910164 polymorphism showed a statistically significant association (P < 0.001) between CC genotype and allele C with SVC (OR = 2.92; 95% CI = 1.56-546). Our findings suggest miRNA-146a SNP (C/G) in our population may be associated with the susceptibility to HBV infection and CC genotype is associated with SVC. Also, the GG genotype and G allele at miRNA-146a rs2910164 is associated with chronic HBV infection in our population.     

Association of PD-L1 gene rs4143815 C>G polymorphism and human cancer susceptibility: A systematic review and meta-analysis

Programmed death ligand 1(PD-L1) mediated immune escape play important roles in the development of cancer. The gene polymorphism of PD-L1, in particular rs4143815 C?>?G, has been associated with the cancer risks, but with conflicting results. Therefore, this meta-analysis was aimed to assess the association between rs4143815 C?>?G and cancer susceptibility. A systematic literature search was performed to select the studies and the pooled odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of association. Eleven eligible studies containing 3711 cases and 3704 controls were enrolled in the meta-analysis. The results suggested that there is a strong association between rs4143815 C?>?G and the cancer risks (G vs. C: OR?=?1.386, 95% CI: 1.132–1.696, p?=?0.002; GG vs. CG?+?CC: OR?=?1.843 95% CI: 1.300–2.613, p?=?0.002; GG?+?CG vs. CC: OR?=?1.280, 95% CI: 1.040–1.576, p?=?0.020). Subgroup analysis based on cancer type suggested that PD-L1 rs4143815 C?>?G might increase the susceptibility to gastric cancer (G vs. C: OR?=?1.842, 95% CI: 1.403–2.418, p?<?0.001) and bladder cancer (G vs. C: OR?=?2.015, 95% CI: 1.556–2.608, p?<?0.001), and genotype GG carriers of PD-L1 rs4143815 C?>?G might have higher risks of HCC (GG vs. CG?+?CC: OR?=?2.226 95% CI: 1.562–3.172, p?<?0.001). PD-L1 rs4143815 C?>?G might confer an increased cancer risk, indicating this SNP may contribute to the pathogenesis of cancer and might be used as a potential biomarker to predict the susceptibility to cancer.     

MicroRNA 146a基因单核苷酸多态性与卵巢上皮性肿瘤易感性的研究

目的 分析microRNA 146a(miR-146a)基因单核苷酸多态(single nucleotide polymorphisms,SNPs)位点rs2910164(G/C)与卵巢上皮性肿瘤易感性的关系.方法 采用病例-对照研究方法,纳入卵巢上皮性肿瘤患者184例为病例组,无卵巢肿瘤病史的人群200例为对照组.使用基因测序方法确定miR-146a基因rs2910164 (G/C)位点的多态基因型,比较不同基因型在病例组和对照组中的分布情况,并对年龄、月经周期、产次、口服避孕药、家族病史因素进行分层研究.结果 在miR-146a基因多态位点rs2910164(G/C)处,病例组和对照组均有GG、GC和CC 3种基因型,且两组的基因型总体分布差异具有统计学意义(P=0.002).与CC基因型相比,GG和GC基因型携带者的卵巢上皮性肿瘤发病风险较低(OR=0.396,95％ CI=0.219～0.717,P=0.002;OR=0.502,95％ CI =0.308～0.818,P=0.006).分层分析显示,这种影响在年龄≤50岁、产次≤2、未口服避孕药、无家族病史的情况下差异显著,x2检验P值分别为:0.001、0.000、0.001、0.001.结论 miR-146a单核苷酸多态位点rs2910164(G/C)与卵巢上皮性肿瘤易感性相关.GG和GC基因型携带者患卵巢上皮性肿瘤的发病风险低于CC基因型携带者.     

Association of two polymorphisms rs2910164 in miRNA-146a and rs3746444 in miRNA-499 with rheumatoid arthritis: A meta-analysis

Background

It has been reported that two single nucleotide polymorphisms (SNPs) rs2910164 in miRNA-146a and rs3746444 in miRNA-499 might be associated with the susceptibility to rheumatoid arthritis (RA). Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two SNPs and RA risk.

Methodology/main results

A systematic search of studies on the association of two SNPs with susceptibility to RA was conducted in PubMed and Embase. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were used to pool the effect size. A total of 6 case-control studies on rs2910164 and 3 studies on rs3746444 were included. Though no evidence of association was found between rs2910164 polymorphism and RA risk in all the genetic models, a trend of reduced risk could be drawn. (C versus G: OR = 0.93, 95% CI 0.82–1.05; GC versus GG: OR = 0.89, 95% CI 0.73–1.10; CC versus GG: OR = 0.84, 95% CI 0.64–1.10; GC/CC versus GG: OR = 0.89, 95% CI 0.73–1.08; CC versus GC/GG: OR = 0.94, 95% CI 0.77–1.14). A significant increased risk of RA was observed in the rs3746444 polymorphism in homozygote comparison, recessive comparison, and allele comparison, but there was insufficient data to fully confirm the association of RA and rs3746444 in miRNA-499.

Conclusions

MiRNA-146a rs2910164 polymorphism is not associated with RA risk, while miRNA-499 rs3746444 polymorphism is correlated with RA risk. However, the results of miRNA-499 rs3746444 should be interpreted with caution due to limited sample and heterogeneity. Large-scale and well-designed studies are needed to validate our findings.     

Predictive role of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) in the development of hepatocellular carcinoma

We conducted a case-control study to evaluate the association of miR-146a rs2910164 (C>G), miR-149 rs2292832 (T>C), miR-196a2 rs11614913 (T>C) and miR-499 rs3746444 (T>C) polymorphisms with the risk of hepatocellular carcinoma. A total of 274 patients with HCC were collected between January 2013 and December 2014. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was taken to determine the polymorphism of miR-146a C>G, miR-149 T>C, miR-196a2 T>C and miR-499 T>C. By comparing with control groups, patients with HCC were more likely to be males (OR=2.01, 95% CI=1.38-2.95), have older age (OR=1.52, 95% CI=1.09-2.13), have a history of alcohol drinking (OR=2.09, 95% CI=1.49-2.93), and be infected with HBV (OR=32.98, 95% CI=19.70-55.46) and HCV (OR=56.26, 95% CI=23.28-152.98) infection. By conditional regression analysis, individuals carrying the TC and CC genotypes of miR-196a2 T>C were found to be associated with an elevated risk of HCC compared to the TT genotype, and the adjusted odds ratio were 1.50 (1.03-2.17) and 2.86 (1.60-5.16), respectively. Moreover, the TC+CC genotype was correlated with an increased risk of HCC (OR=1.69, 95% CI=1.19-2.41) compared to the wide-type genotype. In conclusion, our results suggested that miR-196a2 T>C polymorphism is associated with HCC risk in Chinese population.     

Association of MIR146A rs2910164 variation with a predisposition to sporadic breast cancer in a Pakistani cohort

Single‐nucleotide polymorphisms (SNPs) in genes coding for microRNAs (miRNAs) play a pivotal role in the progression of breast cancer (BC). We investigated the association of miR‐146a rs2910164 GC polymorphism with the risk of BC in the Pakistani population. The miR‐146a rs2910164 polymorphism was genotyped in 300 BC cases and 300 age‐ and gender‐matched healthy controls using T‐ARMS‐PCR. Genotype and allele frequencies were calculated and the association between genotypes and the risk of BC was calculated by odds ratio (OR) and confidence interval (95%). A significant difference in genotypic frequencies (χ² = 63.10; P = <0.0001) and allelic frequencies (OR = 0.3955 (0.3132–0.4993); P = < 0.0001) was observed between cases and controls. Furthermore, we also found that miR‐146 rs2910164 CC homozygote increased the risk of BC in the dominant (OR = 0.2397 (0.1629–0.3526); P = 0.0001; GG vs. GC + CC) and recessive (OR = 2.803 (1.865–4.213); P = <0.0001; CC vs. GC + GG) inheritance models. In summary, miR‐146a rs2910164 GC is significantly associated with BC in the Pakistani population. To our knowledge, this is the first study that assessed MIR146a rs2910164 G > C SNP in Pakistani population. By analyzing the secondary structure of MIR146A variant, a significant structural modification was noted. Study with a larger sample size is needed to further confirm of these findings.     

Association Study of Common Genetic Variants in Pre-microRNAs in Patients with Ulcerative Colitis

Background

Common single-nucleotide polymorphisms (SNPs) in microRNAs (miRNA) have been shown to be associated with susceptibility to several human diseases. We evaluated the associations of three SNPs (rs11614913, rs2910164, and rs3746444) in pre-miRNAs (miR-196a2, miR-146a, and miR-499) with the risk of ulcerative colitis (UC) in a Japanese population.

Methods

The rs11614913 (T?>?C), rs2910164 (C?>?G), and rs3746444 (A?>?G) SNPs were genotyped in 170 UC and 403 control subjects.

Results

The rs3746444 AG genotype was significantly higher among the UC group (odds ratio (OR)?=?1.51, 95% CI?=?1.03?C2.21, p?=?0.037). The rs3746444 AG genotype was associated with onset at an older age (OR?=?1.70, 95% CI?=?1.04?C2.78, p?=?0.035), left-sided colitis and pancolitis (left-sided colitis, OR?=?2.10, 95% CI?=?1.12?C3.94, p?=?0.024; pancolitis, OR?=?1.81, 95% CI?=?1.09?C3.01, p?=?0.028, left-sided colitis?+?pancolitis, OR?=?1.91, 95% CI?=?1.26?C2.92, p?=?0.003), higher number of times hospitalized (OR?=?2.63, 95% CI?=?1.22?C5.69, p?=?0.017), steroid dependence (OR?=?2.63, 95% CI?=?1.27?C5.44, p?=?0.014), and refractory phenotypes (OR?=?2.76, 95% CI?=?1.46?C5.21, p?=?0.002) while the rs3746444 AA genotype was inversely associated with the number of times hospitalized (2??, OR?=?0.36, 95% CI?=?0.17?C0.79, p?=?0.012), steroid dependence (OR?=?0.42, 95% CI?=?0.21?C0.88, p?=?0.021), and refractory phenotypes (OR?=?0.38, 95% CI?=?0.20?C0.72, p?=?0.003). The rs1161913 TT genotype also held a significantly higher risk of refractory phenotype (T/T vs. T/C?+?C/C, OR?=?2.21, 95% CI?=?1.17?C4.18, p?=?0.016).

Conclusions

Our results provided the first evidence that rs3746444 SNP may influence the susceptibility to UC, and both rs3746444 and rs11614913 SNPs may influence the pathophysiological features of UC.     

Genetic variation in miR-100 rs1834306 is associated with decreased risk for esophageal squamous cell carcinoma in Kazakh patients in northwest China

MicroRNAs (miRNAs) are a family of small noncoding RNAs that act as oncogenes and tumor suppressors. Single nucleotide polymorphisms (SNPs) in miRNAs may be associated with changes in phenotype and function. The aim of this study was to verify whether genetic variations in candidate microRNA (miRNA or miR) genes could contribute to esophageal squamous cell carcinoma (ESCC) susceptibility. A case-control study in 248 Kazakh patients with ESCC and 300 frequency matched control subjects was carried out to examine the potential association of six miRNA (miR-100 rs1834306, miR-34b/c rs4938723, miR-375 rs6715345, miR-146a rs2910164, miR-423 rs6505162 and miR-373 rs12983273) polymorphisms with risk of ESCC. We found that miR-100 rs1834306 T>C polymorphism was associated with a significant decreased risk of ESCC. In the recessive model, when the miR-100 rs1834306 TT/TC genotypes were used as the reference group, the CC homozygote genotype was associated with a significant decreased risk for ESCC (adjusted OR=0.495, 95% CI: 0.349-0.702, P=8.05×10^-5). In the dominant model, when the miR-100 rs1834306 TT genotypes was used as the reference group, the TC/CC genotype were associated with a borderline statistically decreased risk for ESCC (adjusted OR=0.665, 95% CI: 0.430-1.031, P=0.067). In addition, the miR-100 rs1834306 C allele in the Kazakh population was significantly associated with decreased risk of ESCC (OR=0.609, 95% CI: 0.48-0.78, P=8.37×10^-5). These findings indicated that functional polymorphism miR-100 rs1834306 C>T might contribute to decreased ESCC risk.     

Genetic study of two single nucleotide polymorphisms within corresponding microRNAs and susceptibility to tuberculosis in a Chinese Tibetan and Han population

MicroRNAs (miRNA) are thought to play important roles in the pathogenesis of diseases. Single nucleotide polymorphisms (SNPs) within miRNAs can change their characteristics via altering their target selection and/or expression, resulting in functional and/or phenotypic changes. We decided to investigate the genetic association with pulmonary tuberculosis with 2 nucleotide variations within corresponding microRNAs regulating the Toll-like receptor (TLR)-mediating signal pathway. MiRNAs potentially regulating the TLR-mediating signal pathway were predicted via bioinformatics. Finally, 2 SNPs, rs2910164 G>C and rs3746444 T>C within miR-146a and miR-499, were selected as candidates in accordance with some criteria. SNPs were genotyped by polymerase chain reaction-restriction fragment length polymorphism and validated by sequencing to demonstrate their association with susceptibility to pulmonary tuberculosis (PTB) in 337 PTB cases and 738 healthy controls, including 318 Tibetan and 757 Han individuals. Bioinformatics databases were searched to support the association between miRNAs and PTB. There was no association between rs3746444 and PTB risk (p = 0.118) in the Han population, but subjects carrying the C allele exhibited decreased PTB risk (odds ratio [OR] = 0.403 [95% confidence interval (95% CI) 0.278-0.583]). However, there was an association between rs3746444 and PTB in the Tibetan population, and individuals carrying the C allele exhibited increased PTB risk (OR = 1.870 [95% CI 1.218-2.871]). A polymorphism (rs2910164 G>C) indicated an association with PTB risk in both Tibetan (p = 0.031) and Han (p = 0.000) populations. However, the role of the G allele of rs2910164, like the C allele in rs3746444, differed in the Tibetan (OR = 1.509, p < 0.05) and Han (OR = 0.575, p < 0.05) groups. This is the first report to suggest that a genetic association with pulmonary tuberculosis with SNPs within the corresponding miRNAs potentially regulates the TLR signal pathway. It is interesting that both the G allele (rs2910164) and the C allele (rs3746444) play different roles in 2 populations. Further functional analysis of the SNP and its impact on mRNA targets is required to confirm the relationship between genotype and phenotype.     

Comprehensive review of genetic association studies and meta-analysis on miRNA polymorphisms and rheumatoid arthritis and systemic lupus erythematosus susceptibility

BackgroundMicroRNAs (miRNAs), small RNA molecules, play a role in the development and differentiation of immune cells in both innate and adaptive immune responses. Our study was aimed to investigate the association between three miRNA polymorphism and rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE) by using meta-analysis approach.MethodsA PubMed database search was conducted during August 2013 to identify case–control studies of miRNAs and RA or SLE risk. Two authors independently extracted information on the study design, the characteristics of the study participants, exposure and outcome assessments. The fix-effects and random-effects models were used for the risk estimates by Stata 11.0 software.ResultsOur meta-analysis of six case–control studies involving a total of 998 RA cases and 1493 controls identified no significant association between mir-146a rs2910164 and RA, with an overall OR of 0.843 (95% CI = 0.642–1.105; CC vs. GG). No association was observed in three studies with a total of 1532 cases and 2168 controls between miR-146a rs2910164 and SLE risk (OR = 0.911, 95% CI = 0.710–1.171; CC vs. GG). Three studies with a total of 529 cases and 595 controls evaluated the mir-499 rs3746444 polymorphism and its association with RA. There was a decreased overall risk of RA under the allelic and genotypic models [OR = 0.616, 95% CI = 0.384–0.981, (T vs. C allele) and OR = 0.386, 95% CI = 0.226–0.659, (TT vs. CC)]. Two studies with 4826 cases and 4181 controls evaluated miR-146a rs57095329 and its association with SLE. There was a significant association between miR-146a rs57095329 and SLE (OR = 1.263, 95% CI = 1.136–1.405, G vs. A allele).ConclusionsThe present meta-analysis suggests important roles for the mir-499 rs3746444 polymorphism in RA, especially in the Caucasian population and for miR-146a rs57095329 polymorphism in SLE. Further studies with large sample size are needed to confirm these associations.     

Association of RIP2 gene polymorphisms and systemic lupus erythematosus in a Chinese population

The aim of this study was to investigate the association of receptor interacting protein 2 (RIP2) single-nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A case-control study was performed on the SNPs rs16900617 and rs16900627 in 590 Chinese SLE patients and 660 healthy controls. These SNPs were typed by TaqMan allele discrimination assays. We found a significant association of rs16900617 G allele [odds ratio (OR) = 0.54, 95% confidence interval (CI) 0.41-0.72] and rs16900627 G allele (OR = 1.28, 95% CI 1.04-1.58) with SLE. Significant differences in genotype frequency distribution were also found in SLE and control individuals (rs16900617: AG versus AA, OR = 0.59, 95% CI 0.44-0.81; GG versus AA, OR = 0.08, 95% CI 0.01-0.65; AG + GG versus AA, OR = 0.55, 95% CI 0.41-0.75; rs16900627: AG versus AA, OR = 1.51, 95% CI 1.17-1.93; AG + GG versus AA, OR = 1.43, 95% CI 1.13-1.82). Analysis of the haplotypes revealed that two haplotypes of AG and GA were also significantly associated with SLE (OR = 1.37, 95% CI 1.11-1.70; OR = 0.60, 95% CI 0.45-0.79). Our findings suggest that the RIP2 gene polymorphisms may be associated with susceptibility to SLE in the Chinese population.     

Hsa-miR-449a genetic variant is associated with risk of gastric cancer in a Chinese population

Gastric cancer (GC) is one of the most common malignancies and one of the major causes of cancer-related deaths worldwide. In the present study, we investigated the association between miR-449a rs112310158 SNP and GC risk. Our findings revealed that a variant GG genotype increased the risk of occurrence of GC compared to a wild type AA genotype (OR = 2.542, 95% CI: 1.304-4.954, P = 0.005). Specifically, the G allele reduced the risk of occurrence of cervical cancer in women compared to the A allele (OR = 1.279, 95% CI: 1.012-1.617, P = 0.043). In conclusion, our findings suggest that miR-449a rs112310158 is a genetic risk factor for GC.     

Genetic association of miRNA-146a with systemic lupus erythematosus in Europeans through decreased expression of the gene

A recent genome-wide association study revealed a variant (rs2431697) in an intergenic region, between the pituitary tumor-transforming 1 (PTTG1) and microRNA (miR-146a) genes, associated with systemic lupus erythematosus (SLE) susceptibility. Here, we analyzed with a case-control design this variant and other candidate polymorphisms in this region together with expression analysis in order to clarify to which gene this association is related. The single-nucleotide polymorphisms (SNPs) rs2431697, rs2910164 and rs2277920 were genotyped by TaqMan assays in 1324 SLE patients and 1453 healthy controls of European ancestry. Genetic association was statistically analyzed using Unphased. Gene expression of PTTG1, the miRNAs miR-3142 and primary and mature forms of miR-146a in peripheral blood mononuclear cells (PBMCs) were assessed by quantitative real-time PCR. Of the three variants analyzed, only rs2431697 was genetically associated with SLE in Europeans. Gene expression analysis revealed that this SNP was not associated with PTTG1 expression levels, but with the microRNA-146a, where the risk allele correlates with lower expression of the miRNA. We replicated the genetic association of rs2341697 with SLE in a case-control study in Europeans and demonstrated that the risk allele of this SNP correlates with a downregulation of the miRNA 146a, potentially important in SLE etiology.     

Association between a promoter polymorphism (rs2192752, –1028A/C) of interleukin 1 receptor,type I (IL1R1) and location of papillary thyroid carcinoma in a Korean population

The interleukin 1 receptor, type I (IL1R1) is important in the pathogenesis of cancer. We investigated whether single nucleotide polymorphisms (SNPs) of IL1R1 contribute to the development of papillary thyroid carcinoma (PTC), in addition to the clinicopathological features such as the size, number, location, extrathyroidal invasion and metastasis of PTC. Three promoter SNPs (rs949963 ?615G/A, rs2192752 ?1028A/C and rs3917225 ?1099A/G) in IL1R1 were genotyped using direct sequencing in 118 patients with PTC and 347 controls. The odds ratio (OR), 95% confidence interval (CI) and P value were analysed using SNPStats and SNPAnalyzer Pro. For the exact results, Fisher’s exact test and Bonferroni correction (P^c) were performed. The three promoter SNPs of IL1R1 were not associated with PTC development. For the clinicopathological features of PTC, rs2192752 was associated with location (one lobe versus both lobes): dominant model, OR = 3.11, 95% CI = 1.39–6.96, P^c = 0.015; log‐additive model, OR = 2.79, 95% CI = 1.38–5.66, P^c = 0.0087. The C allele frequency of rs2192752 was higher in the both lobes group (28.0%) than the one lobe group (12.3%) (OR = 2.77, 95% CI = 1.40–5.48, P^c = 0.009). However, rs949963 and rs3917225 were not correlated with clinicopathological features including location of PTC. The IL1R1 promoter SNP rs2192752 may contribute to the location of PTC, and the C allele of rs2192752 may be a risk factor for the development of PTC in both lobes.     

A Single Nucleotide Polymorphism of IL-21 Gene is Associated with Systemic Lupus Erythematosus in a Chinese Population

The aim of this study was to examine the association of single-nucleotide polymorphisms (SNPs) in IL-21 gene with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. A total of 605 independent SLE patients and 666 unrelated healthy controls were recruited for the case?Ccontrol association study. Two SNPs (rs2221903 and rs907715) within the IL-21 gene intronic region were genotyped by TaqMan SNP allelic discrimination methods. The allele T frequency of SNP rs2221903 in patients and healthy controls was 89.4?% and 86.8?%, respectively [T versus C, odds ratio (OR)?=?1.287, 95?% confidence interval (CI)?=?1.010?C1.640]. No significant differences in genotype frequencies were shown between SLE patients and healthy controls (P value?=?0.705, 0.406, respectively). However, the effect of recessive model (TT versus CC?+?CT, OR?=?1.368, 95?% CI?=?1.050?C1.781) was observed. Distributions of allele and genotype frequencies of the SNP rs907715 showed no significant differences between SLE patients and controls. Analysis of the haplotypes revealed that CC haplotype was significantly associated with SLE (OR?=?0.734, 95?% CI?=?0.573?C0.941). In conclusion, our findings suggest that a SNP (rs2221903) and CC haplotype (rs2221903 and rs907715) of the IL-21 gene is associated with SLE in the Chinese population. However, further studies are needed to determine the functional consequences of this polymorphism with SLE susceptibility.     

CDKAL1基因rs7754860位点G<C多态性与2型糖尿病易感关系的Meta分析*◆

背景：遗传学研究显示2型糖尿病可能存在遗传易感性,但研究结论存在一定的差异。 目的：探讨CDKAL1(细胞周期素依赖激酶5调节亚单位相关蛋白1类似物1)基因rs7754860位点G相似文献   

Association between survivin -31G > C promoter polymorphism and cancer risk: a meta-analysis

Survivin is an inhibitor of apoptosis protein and has a crucial role in the development of cancer. The survivin -31G>C (rs9904341) promoter polymorphism influences survivin expression and has been implicated in cancer risk. However, conflicting results have been published from studies on the association between survivin -31G>C polymorphism and the risk of cancer. To clarify the role of this polymorphism in cancer, we performed a meta-analysis of all available and relevant published studies, involving a total of 3485 cancer patients and 3964 control subjects. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations. The overall results indicated that the variant genotypes were associated with a significantly increased cancer risk (CC vs GG: OR=1.58, 95% CI=1.20-2.10; CC/GC vs GG: OR=1.23, 95% CI=1.00-1.51; CC vs GG/GC: OR=1.51, 95% CI=1.23-1.85). In the stratified analyses, significantly increased risk was associated with the Asian populations (CC vs GG: OR=1.67, 95% CI=1.16-2.40; CC vs GG/GC: OR=1.50, 95% CI=1.17-1.91). We also performed the analyses by cancer type, and no statistical association was observed. The results suggest that the survivin -31G>C promoter polymorphism might be associated with an increased risk of cancer, especially in the Asian populations.     

Impacts of CD152 polymorphisms on cervical cancer susceptibility

AimThe objective of this study was to discuss the effect of CD152 polymorphisms rs231775, rs3087243 and rs5742909 on the susceptibility to cervical cancer.MethodsThe databases of PubMed, EMBASE, Cochrane Library, ISI Web of Science, Google Scholar Web, CNKI and Wanfang were searched for eligible studies. Chi-square-based Q test examined heterogeneity between included studies, and when P_{heterogeneity} was less than 0.05, random-effect model was used to calculate odds ratios (ORs) with their 95 % confidence intervals (95 % CIs); or else, fixed-effect model was selected. Sensitivity analysis was implemented to determine the stability of final results through removing enrolled studies one at a time and then re-obtaining overall estimates. Publication bias among included studies was checked employing Begg’s funnel plot and Egger’s test.ResultsCD152 polymorphism rs231775 decreased cervical cancer risk in total analysis under the genetic models of GG vs. AA, GG vs. AA + AG and G vs. A (OR = 0.73, 95 % CI = 0.59–0.91; OR = 0.78, 95 % CI = 0.65–0.94; OR = 0.92, 95 % CI = 0.87–0.98), and so did the polymorphism rs3087243 in total analysis under the comparisons of AA vs. GG, AA + GA vs. GG, AA vs. GG + GA, A vs. G and GA vs. GG (OR = 0.51, 95 % CI = 0.42–0.60; OR = 0.71, 95 % CI = 0.62–0.82; OR = 0.57, 95 % CI = 0.50–0.66; OR = 0.70, 95 % CI = 0.64–0.77; OR = 0.83, 95 % CI = 0.72–0.97). Besides, the polymorphism rs5742909 elevated the disease onset in total analysis under the contrasts of TT vs. CC, TT + CT vs. CC, TT vs. CC + CT, T vs. C and CT vs. CC (OR = 2.66, 95 % CI = 1.75–4.04; OR = 1.54, 95 % CI = 1.24–1.91; OR = 2.13, 95 % CI = 1.12–4.03; OR = 1.44, 95 % CI = 1.17–1.78; OR = 1.49, 95 % CI = 1.22–1.83).ConclusionCD152 polymorphisms rs231775 and rs3087243 significantly decrease the risk of cervical cancer, while rs5742909 may increase the disease risk.     

The Fc receptor-like 3 gene polymorphisms and susceptibility to autoimmune diseases: An updated meta-analysis

Abstract

Previous studies have identified several single nucleotide polymorphisms (SNPs) of Fc receptor-like 3 (FCRL3), an excellent susceptibility gene, as predisposing factors for human autoimmune diseases (ADs). However, the results remain inconclusive. To assess the effect of four selected SNPs (rs7528684, rs11264799, rs945635 and rs3761959), we conducted a meta-analysis with 34 case-control studies. Summary odd ratios (ORs) and 95% confidence intervals (95% CIs) for the polymorphisms in FCRL3 and ADs risk were evaluated. Furthermore, this meta-analysis was performed by using allele comparisons, as well as stratified analyses by ethnicity and disease phenotypes under different genetic models. Our data showed that the TC, TT?+?TC genotypes of rs7528684 contributed to a lower risk of ADs, compared with the CC carriers (OR?=?0.91, 95% CI?=?0.85–0.97; OR?=?0.91, 95% CI?=?0.85–0.98). In comparison with rs7528684 TC genotype, the TT?+?CC carriers were significantly associated with higher ADs risk (OR?=?1.03, 95% CI?=?1.00–1.07). In terms of stratified analyses by ethnicity and disease phenotypes, there were significant associations of rs7528684 polymorphism both with ADs in Asians and Europeans, and with rheumatoid arthritis, Graves’ disease, type-1 diabetes, and other ADs under different genetic models. Moreover, significant associations were also found to be correlated with ADs risk for the SNP rs11264799 in mixed subgroup, for rs945635 in Europeans, North Americans and mixed group, and for rs3761959 in North Americans. These findings indicate that the polymorphisms in FCRL3 may play a role in the pathogenesis of ADs.