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1.
An international meta-analysis confirms the association of BNC2 with adolescent idiopathic scoliosis.
Ogura, Y, Takeda, K, Kou, I, Khanshour, A, Grauers, A, Zhou, H, Liu, G, Fan, YH, Zhou, T, Wu, Z, et al
Scientific reports. 2018;(1):4730
Abstract
Adolescent idiopathic scoliosis (AIS) is a common spinal deformity with the prevalence of approximately 3%. We previously conducted a genome-wide association study (GWAS) using a Japanese cohort and identified a novel locus on chromosome 9p22.2. However, a replication study using multi-population cohorts has not been conducted. To confirm the association of 9p22.2 locus with AIS in multi-ethnic populations, we conducted international meta-analysis using eight cohorts. In total, we analyzed 8,756 cases and 27,822 controls. The analysis showed a convincing evidence of association between rs3904778 and AIS. Seven out of eight cohorts had significant P value, and remaining one cohort also had the same trend as the seven. The combined P was 3.28 × 10-18 (odds ratio = 1.19, 95% confidence interval = 1.14-1.24). In silico analyses suggested that BNC2 is the AIS susceptibility gene in this locus.
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2.
Association of maternal prenatal smoking GFI1-locus and cardio-metabolic phenotypes in 18,212 adults.
Parmar, P, Lowry, E, Cugliari, G, Suderman, M, Wilson, R, Karhunen, V, Andrew, T, Wiklund, P, Wielscher, M, Guarrera, S, et al
EBioMedicine. 2018;:206-216
Abstract
BACKGROUND DNA methylation at the GFI1-locus has been repeatedly associated with exposure to smoking from the foetal period onwards. We explored whether DNA methylation may be a mechanism that links exposure to maternal prenatal smoking with offspring's adult cardio-metabolic health. METHODS We meta-analysed the association between DNA methylation at GFI1-locus with maternal prenatal smoking, adult own smoking, and cardio-metabolic phenotypes in 22 population-based studies from Europe, Australia, and USA (n = 18,212). DNA methylation at the GFI1-locus was measured in whole-blood. Multivariable regression models were fitted to examine its association with exposure to prenatal and own adult smoking. DNA methylation levels were analysed in relation to body mass index (BMI), waist circumference (WC), fasting glucose (FG), high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), diastolic, and systolic blood pressure (BP). FINDINGS Lower DNA methylation at three out of eight GFI1-CpGs was associated with exposure to maternal prenatal smoking, whereas, all eight CpGs were associated with adult own smoking. Lower DNA methylation at cg14179389, the strongest maternal prenatal smoking locus, was associated with increased WC and BP when adjusted for sex, age, and adult smoking with Bonferroni-corrected P < 0·012. In contrast, lower DNA methylation at cg09935388, the strongest adult own smoking locus, was associated with decreased BMI, WC, and BP (adjusted 1 × 10-7 < P < 0.01). Similarly, lower DNA methylation at cg12876356, cg18316974, cg09662411, and cg18146737 was associated with decreased BMI and WC (5 × 10-8 < P < 0.001). Lower DNA methylation at all the CpGs was consistently associated with higher TG levels. INTERPRETATION Epigenetic changes at the GFI1 were linked to smoking exposure in-utero/in-adulthood and robustly associated with cardio-metabolic risk factors. FUND European Union's Horizon 2020 research and innovation programme under grant agreement no. 633595 DynaHEALTH.
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3.
Circulating Nesfatin-1 Levels and Type 2 Diabetes: A Systematic Review and Meta-Analysis.
Zhai, T, Li, SZ, Fan, XT, Tian, Z, Lu, XQ, Dong, J
Journal of diabetes research. 2017;:7687098
Abstract
The role of nesfatin-1 in glucose homeostasis has been investigated previously. However, although numerous studies have examined the relationships between circulating nesfatin-1 levels and type 2 diabetes, the conclusions are contradictory. We aimed to probe the relationship between circulating nesfatin-1 levels and type 2 diabetes by meta-analysis. Seven studies including 328 type 2 diabetes patients and 294 control subjects were included. Although there was no obvious difference in circulating nesfatin-1 levels between patients with type 2 diabetes and the control group (MD = -0.04; 95% CI = -0.32 to -0.23), subgroup analysis showed higher nesfatin-1 levels in newly diagnosed type 2 diabetes patients (MD = 0.59; 95% CI = 0.45 to 0.74) and significantly lower nesfatin-1 levels in type 2 diabetes patients receiving antidiabetic treatment (MD = -0.26; 95% CI = -0.33 to -0.20). In conclusion, the analysis supports a relationship between circulating nesfatin-1 levels and type 2 diabetes, where newly diagnosed type 2 diabetes was associated with an elevated Nesfatin-1 level, and type 2 diabetes patients receiving antidiabetic treatment showed lower circulating nesfatin-1 levels.
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4.
Polymorphisms in the XPC gene affect urinary bladder cancer risk: a case-control study, meta-analyses and trial sequential analyses.
Sankhwar, M, Sankhwar, SN, Bansal, SK, Gupta, G, Rajender, S
Scientific reports. 2016;:27018
Abstract
Compromised activity of the DNA repair enzymes may raise the risk of a number of cancers. We analyzed polymorphisms in the Xeroderma Pigmentosum, Complementation Group C (XPC) gene for their correlation with urinary bladder cancer. Ala499Val and Lys939Gln polymorphisms were genotyped in 234 urinary bladder cancer cases and 258 control samples. A significant association between Ala499Val polymorphism and bladder cancer was observed (OR = 1.78, CI = 1.19-2.66, p = 0.005); however, Lys939Gln was unrelated (OR = 0.97, CI = 0.65-1.45, P = 0.89). Further analysis revealed that Ala499Val was a significant risk factor only in the presence of smoking (OR = 2.23, CI = 1.28-3.87, p < 0.004) or tobacco chewing (OR = 2.40, CI = 1.43-4.04, p = 0.0008). To further appraise the association, we undertook meta-analyses on seven studies (2893 cases and 3056 controls) on Ala499Val polymorphism and eleven studies (5064 cases and 5208 controls) on Lys939Gln polymorphism. Meta-analyses corroborated the above results, showing strong association of Ala499Val (OR = 1.54, CI = 1.21-1.97, p = 0.001) but not that of Lys939Gln (OR = 1.13, CI = 0.95-1.34, p = 0.171) with urinary bladder cancer risk. In conclusion, XPC Ala499Val substitution increases urinary bladder cancer risk, but Lys939Gln appears to be neutral.
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5.
Associations between XRCC1 Gene Polymorphisms and Coronary Artery Disease: A Meta-Analysis.
Ma, WQ, Han, XQ, Wang, X, Wang, Y, Zhu, Y, Liu, NF
PloS one. 2016;(11):e0166961
Abstract
Genetic variations that influence DNA repair efficiency may contribute to coronary artery disease (CAD) susceptibility. Previous studies have investigated whether there was evidence of an association between polymorphisms at the X-ray repair cross complementing 1 (XRCC1) gene and susceptibility to CAD, but findings have been inconclusive. We identified eligible studies through a comprehensive literature search to determine whether an association exists between XRCC1 gene polymorphisms and CAD susceptibility. Findings were assessed using the odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using a fixed- or random-effects model, based on the heterogeneity of the studies. Ten eligible studies were finally included in this meta-analysis. Our pooled analysis found that XRCC1 polymorphisms were significantly associated with CAD susceptibility under recessive (Arg194Trp: OR = 1.47, 95% CI = 1.13-1.93; Arg399Gln: OR = 1.45, 95% CI = 1.12-1.89), homozygous (Arg194Trp: OR = 1.37, 95% CI = 1.03-1.81; Arg399Gln: OR = 1.56, 95% CI = 1.19-2.05), and allele (Arg399Gln: OR = 1.18, 95% CI = 1.06-1.32) genetic models. Following subgroup analysis by ethnicity, in Asian populations, we found evidence of associations between the XRCC1 Arg194Trp polymorphism and CAD under recessive and homozygous genetic models, and between the XRCC1 Arg399Gln polymorphism and CAD under recessive, homozygous, and allele genetic models. Subgroup analysis stratified by control source revealed associations between the Arg194Trp and Arg399Gln polymorphisms and susceptibility to CAD under recessive and homozygous modes of inheritance, respectively. In addition, subgroup analysis stratified by sample size found that findings of the Arg194Trp polymorphism in large sample sizes were comparable to those found using pooled eligible studies. Based on our meta-analysis, we concluded that the XRCC1 gene polymorphisms, Arg194Trp and Arg399Gln, are associated with CAD susceptibility, specifically in Asian populations. However, additional, comprehensive and well-designed studies are warranted to confirm these findings.
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6.
Association Between X-Ray Cross-complementing Group 3 (XRCC3) Thr241Met Polymorphism and Risk of Thyroid Cancer: A Meta-Analysis.
Lu, W, Wu, G, Zhang, B
Medical science monitor : international medical journal of experimental and clinical research. 2015;:3978-85
Abstract
BACKGROUND The X-ray cross-complementing group 3 (XRCC3) gene encodes a protein that plays an important role in homologous recombination repair (HRR) of DNA double-strand break (DSB). Increasing attention has been drawn to the association of XRCC3 T241M polymorphism with various types of human cancers. In this study, a meta-analysis was performed to investigate whether there is an association between XRCC3 T241M polymorphism and thyroid cancer risk. MATERIAL AND METHODS A comprehensive search was conducted and a total of 8 studies that covered 963 thyroid cancer cases and 1942 controls were included in this analysis. The meta-analysis was performed on both overall database and 2 ethnic subgroups (Caucasian and Asian). The fixed-effects model was used to calculate odds ratio (OR) with 95% confidence intervals (CIs). The publication bias was evaluated using Begg's funnel plots and Egger's test. RESULTS A positive association between XRCC3 T241M polymorphism and thyroid cancer risk was found by the analyses of the overall database using both recessive model (OR=1.40, 95% CI=1.08-1.81, P=0.012) and homozygote comparison (OR=1.41, 95% CI=1.07-1.86, P=0.015), but not by that using the dominant model (OR=1.12, 95% CI=0.95-1.33, P=0.18). However, no significant association of XRCC3 Thr241Met polymorphism with the risk of thyroid cancer was found in individual ethnic subgroups. CONCLUSIONS We conclude that the XRCC3 Thr241Met polymorphism is associated with an increased risk of thyroid cancer in the overall population, while no significant association was observed in individual ethnic subgroups due to limited population size.
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7.
DNA repair gene XRCC3 T241M polymorphism and susceptibility to hepatocellular carcinoma in a Chinese population: a meta-analysis.
Ji, RB, Qian, YS, Hu, AR, Hu, YR
Genetics and molecular research : GMR. 2015;(4):15988-96
Abstract
Numerous studies have evaluated the association between the X-ray repair complementing defective repair in Chinese hamster cells 3 (XRCC3) T241M polymorphism and hepatocellular carcinoma (HCC) risk. However, the results of such investigations have proved inconsistent. Therefore, we performed a meta-analysis of the association between this polymorphism and HCC risk in the Chinese population. Published literature from PubMed and China National Knowledge Infrastructure databases was retrieved, and a total of 5 case-control studies consisting of 2967 patients and 3874 controls were included in this meta-analysis, which revealed a significant association between the XRCC3 T241M polymorphism and HCC risk (TT vs MM: OR = 6.54, 95%CI = 2.14-19.99; TT vs MT: OR = 4.72, 95%CI = 2.26-9.86; dominant model: OR = 0.38, 95%CI = 0.26-0.57; recessive model: OR = 1.27, 95%CI = 0.99-1.62). In a subgroup analysis by sample size (number of subjects > 1000), similar results were obtained. Thus, XRCC3 T241M polymorphism may constitute a risk factor for HCC in the Chinese population.
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8.
Association between the XRCC1 Arg399Gln polymorphism and risk of cervical carcinoma: a meta-analysis.
Liu, DY, Liang, HC, Xiao, XM
Genetics and molecular research : GMR. 2015;(3):9821-8
Abstract
Numerous studies have evaluated the association between Arg399Gln polymorphism of DNA repair gene XRCC1 and cervical carcinoma risk. However, the specific association is still controversial. To assess the relationship between XRCC1 Arg399Gln polymorphism and cervical carcinoma, we conducted a comprehensive meta-analysis of 10 case-control studies with 2051 cervical carcinoma cases and 2919 controls. Meta-analysis results based on all the studies showed a significant association between XRCC1 Arg399Gln polymorphism and cervical carcinoma risk (GlnGln vs ArgArg: OR = 1.29, 95%CI = 0.90-1.85; GlnGln vs ArgGln: OR = 1.15, 95%CI = 0.93-1.43; the dominant model: OR = 0.80, 95%CI = 0.66-0.99; the recessive model: OR = 1.18, 95%CI = 0.93-1.49). In the subgroup analysis by ethnicity, the results also showed significant association between XRCC1 Arg399Gln polymorphism and susceptibility to cervical carcinoma in both Caucasian and Asian populations. The Arg399Gln polymorphism in the XRCC1 gene may be related to the increased risk of cervical carcinoma. Conclusive evidence on the effects of the variants in cervical carcinoma should be addressed in further studies.
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9.
Association of XRCC3 Thr241Met polymorphism and leukemia risk: evidence from a meta-analysis.
Yan, Y, Liang, H, Li, T, Guo, S, Li, M, Qin, X, Li, S
Leukemia & lymphoma. 2014;(9):2130-4
Abstract
UNLABELLED The relationship between the X-ray repair cross-complementing group 3 (XRCC3) Thr241Met (rs861539) polymorphism and the risk of leukemia remains inclusive or controversial. For a better understanding of the effect of XRCC3 Thr241Met (rs861539) polymorphism on leukemia risk, we performed a meta-analysis. All eligible studies were identified through a search of PubMed, Excerpta Medica Database (Embase) and the Chinese Biomedical Literature Database (CBM) up to August 2013. The association between the XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk was analyzed by means of odds ratios (ORs) and 95% confidence intervals (CI). Ultimately, seven studies with 1070 cases and 1850 controls were included in the meta-analysis. There was no association between Thr241Met polymorphism and leukemia risk in any of the five models in the overall populations (T vs. C: OR = 1.43, 95% CI = 0.95-2.13, p = 0.086; TT vs. CC: OR = 1.71, 95% CI = 0.88-3.33, p = 0.112; TC vs. CC: OR = 1.35, 95% CI = 0.96-1.91, p = 0.089; TT vs. TC/CC: OR = 1.59, 95% CI = 0.87-2.89, p = 0.132; TT/TC vs. CC: OR = 1.37, 95% CI = 0.98-1.94, p = 0.070). In subgroup analysis according to ethnicity, a significant association was found between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in Asian but not in Caucasian or mixed populations. In conclusion, the results suggest no association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the overall populations but a significant association between XRCC3 Thr241Met (rs861539) polymorphism and leukemia risk in the Asian population. Considering the limited sample size and ethnicities included in the meta-analysis, further large-scale, well-designed studies are needed to confirm our results.
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10.
The association between the Lys751Gln polymorphism in the XPD gene and the risk of bladder cancer.
Xiong, T, Yang, J, Wang, H, Wu, F, Liu, Y, Xu, R, Lv, Z, Xue, P, Cao, W, Zhang, Y
Molecular biology reports. 2014;(4):2629-34
Abstract
The Lys751Gln polymorphism in the XPD gene have been suggested as a risk factor for bladder cancer, however the results were inconclusive. The aim of the current study is to assess the association by meta-analysis. A total of 15 case-control studies concerning the association between the XPD Lys751Gln polymorphism and bladder cancer risk were included in the meta-analysis. The results suggested that the Lys751Gln polymorphism was not associated with an increased risk of bladder cancer in the dominant model (OR = 1.03, 95 % CI 0.95-1.11, P = 0.53 for Lys/Gln+Gln/Gln vs. Lys/Lys) in overall analysis. In the subgroup analysis by ethnicity, no significant association was found in Caucasians or Asians. Other comparatives suggested a slight significant association between the polymorphism with the risk of bladder cancer in the recessive comparative (OR = 1.14, 95 % CI 1.02-1.29, P = 0.03). The current meta-analysis indicated that the Lys751Gln polymorphism in the XPD gene might be a risk factor for bladder cancer. In the future, more large-scale case-control studies are needed to validate our results.