The rs738409 (I148M) variant of the PNPLA3 gene and cirrhosis: a meta-analysis

The human patatin-like phospholipase domain-containing-3 (PNPLA3) gene rs738409 C>G polymorphism is associated with several types of liver disease. The aim of this meta-analysis was to assess the risk of cirrhosis on the basis of rs738409 allele frequency and genotype. Medline, the Cochrane Library, EMBASE, and Google Scholar were searched for prospective and retrospective studies assessing the effect of the rs738409 polymorphism on liver cirrhosis. Seven studies, involving 2,023 patients with cirrhosis, were included. The G allele was associated with a significantly increased risk of cirrhosis versus the C allele [pooled odds ratio (OR) = 1.86, 95% confidence interval (CI) = 1.64–2.12, Z = 9.55, P < 0.001]. Both the GC and GG genotypes were associated with a significantly increased risk of cirrhosis versus the CC genotype (GC vs. CC: pooled OR = 1.73, 95% CI = 1.51–1.98, Z = 7.86, P < 0.001; GG vs. CC: pooled OR = 3.41, 95% CI = 2.77–4.18, Z = 11.65, P < 0.001). There was no evidence of publication bias. Our findings suggest that patients at risk for liver cirrhosis may benefit from PNPLA3 genotyping and thus more intensive monitoring if the rs738409 C>G polymorphism is identified.     

The PNPLA3 rs738409 148M/M genotype is a risk factor for liver cancer in alcoholic cirrhosis but shows no or weak association in hepatitis C cirrhosis

Background

An isoleucine>methionine mutation at position 148 in the PNPLA3 gene (p.I148M, rs738409) has recently been identified as a susceptibility factor for liver damage in steatohepatitis. Here, we studied whether the PNPLA3 rs738409 polymorphism also affects predisposition to hepatocellular carcinoma (HCC).

Methods

We compared distributions of PNPLA3 genotypes in 80 and 81 Caucasian patients with alcoholic and hepatitis C virus (HCV)-associated HCC to 80 and 81 age- and sex-matched patients with alcohol-related and HCV-related cirrhosis without HCC, respectively. PNPLA3 genotypes in 190 healthy individuals from the same population served as reference. Potential confounders obesity, diabetes, HCV genotype and HBV co-infection were controlled by univariate and multivariate logistic regression with forward variable selection.

Results

PNPLA3 genotypes were in Hardy-Weinberg equilibrium for all study groups. The frequency of the 148M allele was significantly (p<0.001) increased in alcoholic cirrhosis with (53.7%) and without HCC (36.2%) but was not different between healthy controls (22.9%) and patients with cirrhosis (25.3%; p = 0.545) and HCC (30.2%; p = 0.071) due to hepatitis C. HCC risk was highest in 148M/M homozygous patients with alcoholic liver disease (odds ratio (OR) 16.8 versus healthy controls; 95% confidence interval (CI) 6.68–42.43, p<0.001). Finally, multivariate regression confirmed 148M/M homozygosity (OR 2.8; 95%-CI: 1.24–6.42; p = 0.013) as HCC risk factor in alcoholic cirrhosis. In HCV-related cirrhosis only HCV genotype 1 was confirmed as a HCC risk factor (OR 4.2; 95%-CI: 1.50–11.52; p = 0.006).

Conclusion

The PNPLA3 148M variant is a prominent risk factor for HCC in patients with alcoholic cirrhosis, while its effects are negligible in patients with cirrhosis due to HCV. This polymorphism provides an useful tool to identify individuals with particularly high HCC risk in patients with alcoholic liver disease that should be taken into account in future HCC prevention studies.     

Case-control study on association of peroxisome proliferator-activated receptor-δ and SNP-SNP interactions with essential hypertension in Chinese Han population

The aim of this study was to investigate the association of peroxisome proliferator-activated receptor-δ (PPAR-δ) and additional SNP-SNP interaction with essential hypertension (EH) in Chinese Han population. A total of 1248 subjects (625 males, 623 females), including 620 EH patients and 628 normotension subjects, were included in the study. The mean age was 51.2?±?15.1 years old. Logistic regression model was used to examine the association between four SNP and EH; odds ratio (OR) and 95 % confident interval (95 %CI) were calculated. Generalized multifactor dimensionality reduction (GMDR) was employed to analyze SNP-SNP interaction. EH risk was significantly lower in carriers of C allele of the rs2016520 polymorphism than those with TT (TC?+?CC versus TT, adjusted OR (95 %CI)?=?0.61 (0.49–0.78)). In addition, we also found a significant association between rs9794 and EH; EH risk was also significantly lower in carriers of G allele of the rs9794 polymorphism than those with CC (CG?+?GG versus CC, adjusted OR (95 %CI)?=?0.65 (0.53–0.83)). We also found a potential SNP-SNP interaction between rs2016520 and rs9794; subjects with TC or CC of rs2016520 and CG or GG of rs9794 genotype have the lowest EH risk, compared to subjects with TT of rs2016520 and CC of rs9794 genotype; OR (95 %CI) was 0.32 (0.23–0.62) after covariate adjustment. Our results support an important association between rs2016520 and rs9794 minor allele of PPAR-δ and decreased risk of EH and additional interaction between rs2016520 and rs9794.     

Genetic variation in the NBS1 gene is associated with hepatic cancer risk in a Chinese population

NBS1 plays important roles in maintaining genomic stability as a key DNA repair protein in the homologous recombination repair pathway and as a signal modifier in the intra-S phase checkpoint. We hypothesized that polymorphisms of NBS1 are associated with hepatic cancer (HCC) risk. The NBS1 rs1805794 C/G polymorphism has been frequently studied in some cancers with discordant results, but its association with HCC has not been investigated. Moreover, studies of the 3'UTR variant rs2735383 have not touched upon HCC. This study examined the contribution of these two polymorphisms to the risk of developing HCC in a Chinese population. NBS1 genotypes were determined in 865 HCC patients and 900 controls and the associations with risk of HCC were estimated by logistic regression. Compared with the rs1805794 GG genotype, the GC genotype had a significantly increased risk of HCC (adjusted odds ratios [OR]=1.41; 95% confidence interval [CI]=1.11-1.80), the CC carriers had a further increased risk of HCC (OR=2.27; 95% CI=1.68-3.14), and there was a trend for an allele dose effect on risk of HCC (p<0.001). Also, we found that the risk effect of rs1805794 CC+CG was more pronounced in HCC patients that drank (OR=2.28, 95% CI=1.55-3.29 for drinkers; OR=1.31, 95% CI=1.00-1.77 for nondrinkers). However, there was no significant difference in genotype frequencies of rs2735383 G/C site between cases and controls. These findings suggest that rs1805794 C/G polymorphism in NBS1 may be a genetic modifier for developing HCC.     

Association of Ghrelin Gene Polymorphisms and Serum Ghrelin Levels with the Risk of Hepatitis B Virus-Related Liver Diseases in a Chinese Population

Background

The functions of ghrelin (GHRL) include anti-inflammatory effects, reduction of the fibrogenic response, protection of liver tissue, and regulation of cell proliferation. Genetic variations in the GHRL gene may play an important role in the development of chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we investigated whether GHRL gene polymorphisms and its serum levels are associated with hepatitis B virus (HBV)-related diseases risk in a Chinese population.

Methods

176 patients with CHB, 106 patients with HBV-related LC, 151 patients with HBV-related HCC, and 167 healthy controls were recruited in the study. Genotyping of GHRL rs26311, rs27647, rs696217, and rs34911341 polymorphisms were determined with the polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA).

Results

Binary logistic regression analyses adjusting for gender and age revealed that a significant increased risk of LC was found in the GHRL rs26311 GC genotype and combined GC+CC genotypes when compared with the GG genotype (GC vs. GG: OR = 1.671, 95% CI = 1.013–2.757, P = 0.044; GC+CC vs. GG: OR = 1.674, 95% CI = 1.040–2.696, P = 0.034). In subgroup analysis by gender, binary logistic regression analyses adjusting for age showed that the GHRL rs26311 C allele and combined GC+CC genotypes were associated with a significantly increased risk to LC in males (C vs. G OR = 1.416, 95% CI = 1.017–1.972, P = 0.040; GC+CC vs. GG: OR = 1.729, 95% CI = 1.019–2.933, P = 0.042). In addition, we found significant decreased serum GHRL levels in LC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26311 polymorphism with serum GHRL levels in LC patients.

Conclusions

These observations suggest that the GHRL rs26311 polymorphism is associated with an increased risk to HBV-related LC, especially in men. We also found an inverse association of serum GHRL levels with LC.     

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.     

Association of <Emphasis Type="Italic">BLK</Emphasis> (rs13277113, rs2248932) polymorphism with systemic lupus erythematosus: a meta-analysis

The B-cell lymphocyte kinase (BLK) is a src-family protein tyrosine kinase specifically expressed in B-lineage cells that has been implicated in the pathogenesis of systemic lupus erythematosus (SLE) and has been investigated in numerous ethnically diverse studies. However, genetic association studies that have examined the association between BLK gene variants and SLE have produced conflicting results. To shed further light on this issue, we performed a meta-analysis of the association between rs13277113, rs2248932 polymorphism and SLE in different ethnic groups. An updated literature-based meta-analysis of six original articles involving 20,271 control individuals and 11,796 subjects with SLE was conducted. Crude ORs with 95% CIs were used to assess the strength of association between rs13277113, rs2248932 polymorphism and SLE risk. Publication bias was estimated using Egger’s linear regression test. The authors assessed the evidence of genotypic association using STATA Version 10.0. The combined overall odds ratio, calculated for SLE and the risk A-allele of rs13277113 was 1.416 (95% CI: 1.358, 1.477). An odds ratio of 1.264 (95% CI: 1.208, 1.322) was found for the T-allele of rs2248932. Significant associations of rs13277113 and SLE were observed for dominant model (AA + AG vs. GG, OR: 1.518; 95% CI: 1.411, 1.632), and recessive model (AA vs. AG + GG, OR: 1.553; 95% CI: 1.461, 1.651); so were rs2248932 and SLE for dominant model (TT + TC vs. CC, OR: 1.342; 95% CI: 1.233, 1.460), and recessive model (TT vs. TC + CC, OR: 1.338; 95% CI: 1.257, 1.424). All of these were conducted in fixed effects model as heterogeneity was not detected. Tests for bias revealed no evidence of biases. On the assessment of available evidence, the authors concluded that moderate evidence exists for an association between the BLK rs13277113, rs2248932 variants and SLE. Therefore, further research is warranted on the role of BLK polymorphisms in the etiology of SLE.     

The genetic polymorphisms of intercellular cell adhesion molecules and breast cancer susceptibility: a meta-analysis

Intercellular cell adhesion molecules (ICAMs) genetic polymorphisms have been considered to be implicated in the development of breast cancer. However, the previous reports are conflicting. Therefore, we performed a meta-analysis to assess the association between three polymorphisms, including ICAM1 K469E, ICAM5 V301I, ICAM5 rs281439, and breast cancer risk. The meta-analyses are based on a literature search of PubMed, CNKI and VIP database up until August 2011. Pooled odds ratio (OR) with 95 % confidence interval (CI) was calculated using review manager 5.0.25 package. In total, five populations (2,020 cases and 2,012 controls) on ICAM1 K469E polymorphism, four populations (1,797 cases and 2,244 controls) on ICAM5 V301I polymorphism and five populations (2,744 cases and 3,006 controls) on ICAM5 rs281439 variant were included. Overall, the meta-analysis showed no significant association between ICAM1 K469E polymorphism and breast cancer risk. However, a significant association was observed for ICAM5 V301I polymorphism (VV vs. II: OR = 1.48, 95 % CI 1.04–2.13, P = 0.03; VV/VI vs. II: OR = 1.25, 95 % CI 1.05–1.48, P = 0.01). In addition, there was a significant association between ICAM5 rs281439 variant and breast cancer risk (GG vs. CC: OR = 1.31, 95 % CI 1.03–1.65, P = 0.03). Our meta-analysis suggests that the ICAM5 V301I and rs281439 variants but not ICAM1 K469E polymorphism may contribute to the susceptibility of breast cancer. Given the limited sample sizes, further investigation is needed.     

The association of rs1149048 polymorphism in Matrilin-1(MATN1) gene with adolescent idiopathic scoliosis susceptibility: a meta-analysis

Several previous studies have evaluated the association between rs1149048 polymorphism in the matrilin-1 gene (MATN1) and the risk of adolescent idiopathic scoliosis (AIS). However the results of those studies were inconsistent. We conducted this meta-analysis to assess whether rs1149048 polymorphism was involved in the risk of AIS and evaluated the associations in different ethnicities. Electronic databases, such as: PubMed, EMBASE, WANFANG databases in any languages up to Dec 2012 were searched to assess the association between rs1149048 polymorphism and AIS. Meta-analysis was performed by STATA 12.0 software to estimate the pooled odds ratio (OR) and the 95 % confidence interval (CI). Finally four papers including five studies which involved 1436 AIS patients and 1,879 controls were identified for this meta-analysis. The results showed that G allele of the rs1149048 was significantly associated with increased AIS risk [OR = 1.13, 95 % CI (1.02–1.25), P = 0.023]. As for genotype (GG vs. GA + AA), homozygous GG genotype was also found to be a risk factor of developing AIS. The subgroup meta-analysis results showed G allele and GG genotype were significantly associated with AIS in Asian group but not in Caucasian group. Neither Egger’s test nor Begg’s test found evidence of publication bias in current study (P > 0.05). In summary, this meta-analysis found an overall significant association of rs1149048 polymorphism with risk of AIS, especially in Asian population. The relationship between rs1149048 polymorphism and AIS in other ethnic population is needed to be investigated.     

IL-6-174 G/C and -572 C/G polymorphisms and risk of Alzheimer's disease

Associations between interleukin 6 (IL-6) polymorphisms and Alzheimer's disease (AD) remain controversial and ambiguous. The aim of this meta-analysis is to explore more precise estimations for the relationship between IL-6-174 G/C and -572 C/G polymorphisms and risk for AD. Electronic searches for all publications in databases PubMed and EMBASE were conducted on the associations between IL-6 polymorphisms and risk for AD until January 2012. Odds ratio (OR) and 95% confidence intervals (CIs) were calculated using fixed and random effects models. Twenty-seven studies were included with a total of 19,135 individuals, involving 6,632 AD patients and 12,503 controls. For IL-6-174 G/C polymorphism, the combined results showed significant differences in recessive model (CC vs. CG+GG: OR?=?0.65, 95%CI?=?0.52-0.82). As regards IL-6-572 C/G polymorphism, significant associations were shown in dominant model (CG+GG vs. CC: OR=?0.73, 95% CI?=?0.62-0.86) and in additive model (GG vs. CC, OR=?0.66, 95% CI?=?0.46-0.96). In conclusion, genotype CC of IL-6-174 G/C and genotype GG plus GC of IL-6-572 C/G could decrease the risk of AD.     

Meta-Analysis of MicroRNA-146a rs2910164 G>C Polymorphism Association with Autoimmune Diseases Susceptibility,an Update Based on 24 Studies

Background

Published data showed that the susceptibility of autoimmune diseases (ADs) was associated with the polymorphism rs2910164 in microRNA-146a (miR-146a). However, the results remain controversial so far. Two meta-analyses published in 2013 and 2014 came to opposite conclusions. In order to derive a more precise estimation of the relationship, we performed this meta-analysis.

Methods

We searched the PubMed, OvidSP and CNKI databases (published prior to September 8th, 2014) and extracted data from eligible studies. The procedure of meta-analysis was performed by using the Stata 12.0 software. Random effect model or fixed effect model were chosen respectively, according to the between study heterogeneities.

Results

A total of 24 case-control studies, 11 more than previous meta-analysis on this topic, were involved. We took stratified analyses by different ethnicities and different types of diseases in different genetic models. In Caucasian subgroup, significant increased risks of GC genotype and GC+CC genotype with ADs susceptibility were found in heterozygote model (GC vs GG, OR = 1.38, 95% CI 1.04–1.83, p = 0.024) and dominant model (GC+CC vs GG, OR = 1.37, 95% CI 1.01–1.85, p = 0.041), respectively. Meanwhile, in other disease subgroup, significant increased risks of C allele, CC genotype and GC+CC genotype were found in allele model (C vs G, OR = 1.16, 95% CI 1.04–1.31, p = 0.010), homozygote model (CC vs GG, OR = 1.42, 95% CI 1.10–1.84, p = 0.006) and dominant model (GC+CC vs GG, OR = 1.25, 95% CI 1.04–1.51, p = 0.020), respectively.

Conclusions

MiR-146a rs2910164 G>C polymorphism was associated with the susceptibility of ADs.     

A nonsynonymous gene variant in the adiponutrin gene is associated with nonalcoholic fatty liver disease severity

We explored the role of the adiponutrin (PNPLA3) nonsynonymous-rs738409 single nucleotide polymorphism (SNP) in genetic susceptibility to nonalcoholic fatty liver disease (NAFLD) and whether this SNP contributes to the severity of histological disease. Two hundred sixty-six individuals were evaluated in a case-control association study, which included 172 patients with features of NAFLD and 94 control subjects. The rs738409 G allele was significantly associated with NAFLD (P < 0.001; OR 2.8 95%, CI 1.5–5.2), independent of age, sex, body mass index (BMI), and Homeostasis Model Assessment (HOMA) index. When we tested the hypothesis of a relation between the SNP and the histological spectrum of NAFLD, a significant association was observed [chi2 19.9, degree of freedom (df): 2, P < 5 × 10⁻⁵, adjusted for HOMA and BMI]. The degree of liver steatosis, as evaluated by liver biopsy, was significantly associated with the rs738409 G allele. Patients with CC genotype showed a lower steatosis score (14.9% ± 3.9) in comparison with the CG genotype (26.3% ± 3.5) and GG genotype (33.3% ± 4.0) (P < 0.005). The proportion of the total variation attributed to rs738409 genotypes was 5.3% (β 0.23 ± 0.07; P < 0.002). Our data suggest that the rs738409 G allele is associated not only with fat accumulation in the liver but also with liver injury, possibly triggered by lipotoxicity.     

A multi-ethnic study of a PNPLA3 gene variant and its association with disease severity in non-alcoholic fatty liver disease

The adiponutrin (PNPLA3) rs738409 polymorphism has been found to be associated with susceptibility to non-alcoholic fatty liver disease (NAFLD) in various cohorts. We further investigated the association of this polymorphism with non-alcoholic steatohepatitis (NASH) severity and with histological features of NAFLD. A total of 144 biopsy-proven NAFLD patients and 198 controls were genotyped for PNPLA3 gene polymorphism (rs738409 C>G). The biopsy specimens were histologically graded by a qualified pathologist. We observed an association of G allele with susceptibility to NAFLD in the pooled subjects (OR 2.34, 95% CI 1.69-3.24, p < 0.0001), and following stratification, in each of the three ethnic subgroups, namely Chinese, Indian and Malay (OR 1.94, 95% CI 1.12-3.37, p = 0.018; OR 3.51, 95% CI 1.69-7.26, p = 0.001 and OR 2.05, 95% CI 1.25-3.35, p = 0.005, respectively). The G allele is associated with susceptibility to NASH (OR 2.64, 95% CI 1.85-3.75, p < 0.0001), with NASH severity (OR 1.85, 95% CI 1.05-3.26, p = 0.035) and with presence of fibrosis (OR 1.95, 95% CI 1.17-3.26, p = 0.013) but not with simple steatosis nor with other histological parameters. Although the serum triglyceride level is significantly higher in NAFLD patients compared to controls, the G allele is associated with decreased level of triglycerides (p = 0.029) in the NAFLD patients. Overall, the rs738409 G allele is associated with severity of NASH and occurrence of fibrosis in patients with NAFLD.     

Association of PNPLA3 rs738409 polymorphism with liver steatosis but not with cirrhosis in patients with HBV infection: Systematic review with meta‐analysis

Background

Hepatitis B virus (HBV) infection is a worldwide health issue and is well known for being the main cause of developing secondary liver complications such as cirrhosis and hepatocellular carcinoma (HCC). The PNPLA3 rs738409 polymorphism has been investigated conclusively with occurrence risk of steatosis and cirrhosis. Therefore, performing a meta‐analysis of the available studies with the aim of clarifying the association between rs738409 and occurrence risk of steatosis and cirrhosis among HBV‐infected patients would be helpful.

Methods

Chronic HBV infection was defined as the persistence of HBsAg for more than 6 months. To gather sufficient data for this meta‐analysis, reliable databases were conclusively searched using appropriate keywords. Only studies that satisfied the inclusion criteria were enrolled in the present study.

Results

This meta‐analysis pooled four studies with 1135 cases of chronic hepatitis B (CHB) to evaluate the impact of PNPLA3 SNP on liver steatosis and also pooled five studies with 3713 cases of CHB to evaluate the impact of PNPLA3 SNP on cirrhosis. The association of rs738409 with each complication was investigated. The rs738409 was found to be associated with steatosis in recessive [p = 4.57 × 10^–6, odds ratio (OR) = 2.85], dominant (p = 4.35 × 10^‐6, OR = 1.84), co‐dominant (p = 6.18 × 10^‐8; OR = 3.74) and allelic (p = 9.79 × 10^‐9; OR = 1.78) models. No association was found between rs738409 and cirrhosis development in recessive (p = 0.99, OR = 1.00), dominant (p = 0.30, OR = 0.92), co‐dominant (p = 0.74; OR = 0.96) and allelic (p = 0.45; OR = 0.96) models.

Conclusions

Although the PNPLA3 rs738409 G allele has been associated with the risk of steatosis in CHB patients, no association between this polymorphism and the risk of cirrhosis was seen.     

The association between MTHFR C677T polymorphism and ovarian cancer risk: a meta-analysis of 18, 628 individuals

Methylenetetrahydrofolate reductase (MTHFR) enzyme plays an important role in folate metabolism and MTHFR polymorphisms have been suggested to be associated with risk of various cancers. MTHFR C677T polymorphism is a common genetic alteration and may affect the host susceptibility to ovarian cancer. The aim of this study was to investigate the association between MTHFR C677T polymorphism and ovarian cancer risk by performing a meta-analysis. Pubmed, Embase, Web of Science and Chinese Biomedical Database (CBM) databases were searched for case–control studies investigating the association between MTHFR C677T polymorphism and ovarian cancer. Odds ratio (OR) and its 95 % confidence interval (95 % CI) was used to assess this possible association. 13 individual case–control studies from 10 publications with a total of 18, 628 subjects (5, 932 cases and 12, 696 controls) were included into this meta-analysis. Meta-analyses showed there was no association between MTHFR C677T polymorphism and ovarian cancer risk in Caucasians under all five genetic models (All P values for the pooled ORs were more than 0.05), whereas there was an obvious association between MTHFR C677T polymorphism and ovarian cancer risk in Asians under four genetic models (for T vs C, OR (95 % CI) = 1.38(1.19–1.61); for TT vs CC, OR (95 % CI) = 2.32(1.63–3.29); for TT vs TC+CC, OR (95 % CI) = 2.04(1.47–2.85); for TT+TC vs CC, OR (95 % CI) = 1.36(1.12–1.65)). Subgroup analyses suggested ethnicity was the major source of heterogeneity. This meta-analysis supports an association between MTHFR C677T polymorphism and ovarian cancer risk, and there might be a race-specific effect in this association. Further studies with large sample size and careful design are needed to identify this association more comprehensively.     

The association between common genetic variant of microRNA-146a and cancer susceptibility

Published data on the association between microRNA-146a (miR-146a) G/C polymorphism and cancer susceptibility are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 23 studies including 10,585 cases and 12,183 controls were used in the meta-analysis. Overall, no significant associations were found between miR-146a G/C polymorphism and cancer risk when all studies pooled into the meta-analysis (GC vs. CC: OR=1.08, 95% CI=0.94-1.24; GG vs. CC: OR=1.13, 95% CI=0.93-1.37; dominant model: OR=1.09, 95% CI=0.94-1.26). In the subgroup analysis by ethnicity, still no significant associations were found. In the subgroup analysis by cancer type, statistically significantly increased risks were found for papillary thyroid carcinoma (GC vs. CC: OR=3.44, 95% CI=1.86-6.34; GG vs. CC: OR=2.20, 95% CI=1.22-3.99; dominant model: OR=2.68, 95% CI=1.48-4.83). In the subgroup analysis by population-based controls or hospital-based controls, no statistically significantly increased risks were found. Despite some limitations, this meta-analysis suggests that the miR-146a G allele is a low-penetrant risk factor for papillary thyroid carcinoma development.     

XRCC1 Arg399Gln genetic polymorphism and the risk of hepatocellular carcinoma: a meta-analysis

The X-ray repair cross-complementing group 1 (XRCC1) gene, one of over 20 genes that participate in the base excision repair pathway, is thought to account for differences in susceptibility to hepatocellular carcinoma. To assess the relationship between the XRCC1 Arg399Gln polymorphism and the risk of hepatocellular carcinoma (HCC), we performed a meta-analysis. All the relevant studies were extracted from PubMed, Embase, the Chinese biomedicine databases, the Chinese national knowledge infrastructure, and the Wanfang databases (prior to August 2012). The meta-analysis was performed using all eligible studies, which covered a total of 2,554 cases and 3,320 controls, to examine the association between XRCC1 Arg399Gln polymorphism and the risk of HCC. Our analysis suggested that the variant genotypes of the XRCC1 Arg399Gln gene were associated with a significantly increased risk of HCC in a co-dominant model (Arg/Gln vs. Arg/Arg, odd ratios [OR] 1.39, 95 % confidence interval [CI] 1.08–1.79; Gln/Gln vs. Arg/Arg, OR 1.26, 95 % CI 1.04–1.52) and a dominant model (Arg/Gln + Gln/Gln vs. Arg/Arg OR 1.36, 95 % CI 1.07–1.72), whereas no association was observed in the recessive model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.05, 95 % CI 0.91–1.21). The results of the subgroup analysis by ethnicity indicated that the XRCC1 Arg399Gln polymorphism was associated with increased risk of HCC in Asian populations using the co-dominant model (Arg/Gln vs. Arg/Arg, OR 1.41, 95 % CI 1.06–1.87) and the dominant model (Gln/Gln vs. Arg/Gln + Arg/Arg, OR 1.35, 95 % CI 1.03–1.76). Our analysis provides evidence that the XRCC1 Arg399Gln polymorphism may be associated with a higher risk of HCC, especially among Asian populations.