ObjectiveTo systematically review the relationship between T309G polymorphism of murine double minute 2 (MDM2) gene and susceptibility of prostate cancer. MethodsThe PubMed, Embase, WanFang Data, CNKI databases were electronically searched to collect case-control studies related to the objectives from inception to May, 2023. Two reviewers independently screened literature, extracted data and assessed the risk of bias of the included studies. Meta-analysis was then performed by using Stata 14.0 software. ResultsA total of 10 studies involving 5 781 patients and 5 477 healthy controls were included. The results of meta-analysis showed that the MDM2 gene T309G polymorphism was not associated with preeclampsia (allele model G vs. T: OR=0.89, 95%CI 0.77 to 1.04, P=0.13; homozygote model GG vs. TT: OR=0.86, 95%CI 0.64 to 1.16, P=0.32; heterozygote model TG vs. TT: OR=1.04, 95%CI 0.86 to 1.26, P=0.12; dominant model GG+TG vs. TT: OR=0.96, 95%CI 0.89 to 1.04, P=0.36; recessive model GG vs. TG+TT: OR=0.84, 95%CI 0.63 to 1.14, P=0.27). The results of subgroup analysis based on ethnicity and source of control were similar to the overall results. Sensitivity analysis showed that the results were robust. Conclusion Current evidence shows that the MDM2 gene T309G polymorphism is not associated with prostate cancer susceptibility. Due to the limited quality and quantity of the included studies, more high quality studies are needed to verify the above conclusion.
Objective To systematically evaluate the correlation between endometriosis (EM) in Chinese women and Xba I polymorphism in intron-1 of estrogen receptor α (ER-α) gene. Methods Such databases as PubMed, MEDLINE, The Cochrane Library (Issue 3, 2012), VIP, CBM, WanFang Data and CNKI were searched to collect case-control studies about the correlation between EM and Xba I polymorphism in intron-1 of ER-α gene. The retrieval time was from 1980 to 2012. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data and assessed the quality, and then the meta-analysis was conducted by using RevMan 5.0 and Stata 12.0 software. Results A total of 7 studies involving 676 EM patients and 688 healthy volunteers were included. The results of meta-analyses showed that Chinese women with X/X genotype had similar risk of EM compared to those with x/x genotype (OR=0.95, 95%CI 0.58 to 1.54, P=0.82) or X/x genotype (OR=0.73, 95%CI 0.44 to 1.20, P=0.22). The allele X also showed similar risk of EM compared to the allele x (OR=1.11, 95%CI 0.93 to 1.33, P=0.25). Conclusion At present, it has not yet been found that the incidence of EM in Chinese women is related to the Xba I polymorphism in intron-1 of ER-α gene as well as the allele X. For the quantity and quality limitation of the included studies, this conclusion has to be proved by more studies.
ObjectiveTo explore the relationship between the -2548 G/A functional polymorphism in the 5′ promoter region of the leptin gene and gallstones. Methods The -2548 G/A polymorphisms of leptin gene were determined by polymerase chain reactionrestriction fragment length polymorphism technology (PCRRFLP) in 118 patients with cholesterol gallstones and 53 normal control subjects. Then the allele and genotype distribution were studied. Results The distribution of leptin2458 G/A in two groups was statistically significantly different: the genotype frequency of AA+GA of patients in gallstone group was higher than that in control group (χ2=4.251, P=0.039). AA+AG genotype had 2.813 times greater risk for gallstone disease compared with GG genotype (OR=2.813, 95% CI=1.020-7.757). Allele frequency distribution in the two groups was different: the allele frequency of A of patients in gallstone group was higher than that in control group (χ2=5.791, P=0.016). The risk of gallstone disease in the A alleles carriers was 1.777 times as higher as the carriers of G alleles (OR=1.777, 95% CI=1.110-2.844). ConclusionThe -2548 G/A polymorphism in the 5′ promoter region of leptin gene is significantly correlated with the gallstones. The A alleles of leptin may be a genetic factor which contributes to individual susceptibility for gallstone, while the G alleles of leptin may be a genetic factor that prevents people from gallstone.
Objective To systematically review the correlation between epidermal growth factor (EGF) 61A/G polymorphism and the risk of esophageal carcinoma. Methods Such databases as PubMed, EMbase, CJFD, CBM, CNKI, VIP and WanFang Data were electronically searched from inception to January 1st, 2013, to collect case-control studies on the correlation between epidermal growth factor (EGF) 61A/G polymorphism and the risk of esophageal carcinoma. Two reviewers independently identified the literature according to inclusion and exclusion criteria, extracted data, and assessed the quality of the included studies. Then, meta-analysis was performed using RevMan 5.1 and Stata 12.0 software. Results A total of six studies involving 1 448 cases and 1 728 control subjects were included. The results of meta-analysis showed that, there was no significant association between EGF 61A/G polymorphism and the risk of esophageal carcinoma (dominant model: AG+GG vs. AA: OR=1.22, 95%CI 0.91 to 1.65; and recessive model: GG vs. AG+AA: OR=1.35, 95%CI 0.94 to 1.94; AG vs. AA: OR=1.12, 95%CI 0.93 to 1.35; GG vs. AA: OR=1.43, 95%CI 0.83 to 2.47). The results of subgroup analysis grouped by ethnicity showed that, EGF 61A/G polymorphism increased the risk of esophageal carcinoma of the White population (dominant model: AG+GG vs. AA: OR=1.39, 95%CI 1.14 to 1.71; and recessive model: GG vs. AG+AA: OR=1.75, 95%CI 1.37 to 2.25; GG vs. AA: OR=1.93, 95%CI 1.47 to 2.55). However, it had no correlation to the risk of esophageal carcinoma of Asian population. Conclusion Current studies showed that, EGF 61A/G polymorphism is not associated with susceptibility to esophageal carcinoma , but it may increase the risk of esophageal carcinoma in White population. Due to limited quality and quantity of the included studies, the above conclusion needs to be verified by more studies with large sample size.
ObjectiveTo systematically review the association between C677T and A1298C polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene and the risk of unexplained recurrent spontaneous abortion (URSA). MethodsWe searched PubMed, EMbase, CBM, CNKI, VIP and WanFang Data from inception to May 2015 to collect case-control studies about the association between the MTHFR gene C677T and A1298C polymorphisms and the risk of URSA. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.0 and Stata 12.0 software. ResultsA total of 42 case-control studies involving 3 970 URSA patients and 5 297 controls were included. The results of meta-analysis showed that MTHFR C677T polymorphism was associated with the increased risk of URSA (T vs. C: OR=1.34, 95% CI 1.16 to1.54, P < 0.000 01; TT vs. TC+CC: OR=1.70, 95% CI 1.36 to 2.12, P < 0.000 01; TT+TC vs. CC: OR=1.34, 95% CI 1.11 to 1.62, P=0.002; TC vs. CC: OR=1.19, 95% CI 0.99 to 1.43, P=0.061; TT vs. CC: OR=1.95, 95% CI 1.48 to 2.56, P < 0.000 01). Subgroup analysis by ethnicity indicated that the MTHFR C677T polymorphism was associated with the increased risk of URSA in east Asians (T vs. C: OR=1.61, 95% CI 1.39 to 1.87, P < 0.000 01; TT vs. TC+CC: OR=2.05, 95% CI 1.54 to 2.71, P < 0.000 01; TT+TC vs. CC: OR=1.76, 95% CI 1.41 to 2.19, P < 0.000 01; TC vs. CC: OR=1.53, 95% CI 1.21 to 1.94, P < 0.000 01; TT vs. CC: OR=2.77, 95% CI 1.94 to 3.97, P < 0.000 01) but was not associated with the increased risk of URSA in Caucasians. The results of meta-analysis also showed that there was no significant association between the MTHFR A1298C polymorphism and the URSA in all population. ConclusionCurrent evidence indicates that significant association is found between MTHFR C677T mutation and URSA in east Asians but not in Caucasians. Further study indicates that women carrying TT or TC gene significantly increases the risk of URSA and TT mutant gene carriers have a higher URSA risk. There is no significant association between MTHFR A1298C mutation and URSA in all population. Due to the quantity and quality limitations of included studies, more high quality case-control or cohort studies are needed to verify the above conclusions.
ObjectivesTo investigate the correlation of warfarin dose genetic and polymorphism of Han-patients after heart valve replacement, to forecast the anticoagulation therapy with warfarin reasonable dosage, and to realize individualized management of anticoagulation monitoring. MethodsWe selected 103 patients between January 1, 2011 and December 31, 2012 in West China Hospital of Sichuan University who were treated by oral warfarin after heart valve replacement with monitoring anticoagulation by international normalized ratio (INR) in Anticoagulation Therapy Database of Chinese Patients after Heart Valve Replacement. There were 32 males and 71 female at age of 21-85 (48.64± 11.66) years. All the patients' CYP2C9 and VKORC1 genetic polymorphisms were detected by using polymerase chain reaction-restriction fragment length polymorphism (PCR-RELP) method and gene sequencing technology. Warfarin concentration in plasma was determined by high performance liquid chromatography (HPLC) method. The activity of coagulation factorⅡ, Ⅶ, Ⅸ, Ⅹwas determined by Sysmex CA7000 analyzer. ResultsThe multivariate linear regression analysis showed that age, body surface area, and coagulation factor activity had no significant effect on warfarin dosage. While the gene polymor-phisms of CYP2C9 and VKORC1, warfarin concentration, and age had significant contributions to the overall variability in warfarin dose with decisive coefficients at 1.2%, 26.5%, 43.4%, and 5.0% respectively. The final equation was:Y=1.963-0.986× (CYP2C9* 3) +0.893× (VKORC1-1639) +0.002× (warfarin concentration)-0.019× (age). ConclusionMultiple regression equation including gene polymorphisms of CYP2C9 and VKORC1, non-genetic factors of coagulation factor activity, warfarin concentration, age, and body surface area can predict reasonable dosage of warfarin for anticoagulation to achieve individualized management of anticoagulation monitoring and reduce the anticoagulation complications.
ObjectiveTo explore the associations between estrogen receptor α (ESR1) gene intron 1 PvuⅡ (−397 T/C, rs2334693), XbaⅠ (−351 A/G, rs9340799) polymorphisms and premature ovarian failure (POF).MethodsLiterature published before February 2021 were retrieved in PubMed, Web of Science, China National Knowledge Infrastructure, Wanfang, and CQVIP databases, according to the inclusion and exclusion criteria developed before. Odds ratio (OR) and 95% confidence interval (CI) were used for data analysis, the Q test and I2 statistic were used for heterogeneity analysis. Random-effect model or fixed-effect model was used according to I2 value. All analyses were performed by RevMan 5.3 software.ResultsSix case-control studies were included in this meta-analysis. For the associations between ESR1 gene intron 1 PvuⅡ polymorphisms and POF, there was no statistical difference in TT vs. CC model [OR=0.72, 95%CI (0.31, 1.70), P=0.46], TC vs. CC model [OR=1.09, 95%CI (0.83, 1.43), P=0.54], recessive model [OR=1.08, 95%CI (0.68, 1.70), P=0.74], or dominant model [OR=0.77, 95%CI (0.42, 1.42), P=0.41]. For the associations between ESR1 gene intron 1 XbaⅠ polymorphisms and POF, there was no statistical difference in AA vs. GG model [OR=0.88, 95%CI (0.44, 1.75), P=0.72], AG vs. GG model [OR=1.23, 95%CI (0.84, 1.79), P=0.29], recessive model [OR=1.14, 95%CI (0.81, 1.61), P=0.44], or dominant model [OR=0.75, 95%CI (0.41, 1.35), P=0.34], either. No statistical difference was found in the ethno-based subgroup analyses (P>0.05). Most models had obvious heterogeneities.ConclusionsCurrent evidence can’t confirm the associations between ESR1 gene PvuⅡ, XbaⅠ polymorphisms and POF. High-quality, multi-central and large-sample studies are still necessary to support this conclusion.
ObjectiveTo investigate the distribution of uridine diphosphate-glucuronosyltransferase 1A1 (UGT1A1) gene polymorphisms in esophageal carcinoma (EC) patients, and their relationship with adverse effects (delayed diarrhea and neutropenia) of Irinotecan. MethodsForty-eight patients with esophageal squamous carcinoma who were admitted to Sichuan Provincial People's Hospital between January and October 2012 were recruited in the study. There were 37 male and 11 female patients with their age of 56 (25-38) years. Formalin-fixed, paraffin-embedded samples were collected from those EC patients and genomic DNA was extracted. UGT1A1 polymorphisms were detected by PCR and DNA sequencing. Three genetic loci were investigated including UGT1A1* 28 (TA6 > TA7), UGT1A1* 6 (211G > A) and UGT1A1* 93 (-3156G > A). Adverse effects (delayed diarrhea and neutropenia) of patients with different UGT1A1 polymorphisms after Irinotecan treatment were recorded. The relationship between UGT1A1 polymorphisms and Irinotecan-induced adverse effects was analyzed. ResultsUGT1A1 polymorphisms were detected in 10 out of 48 (20.8%) EC patients. UGT1A1* 93 (-3156G > A)polymorphisms were most common with the polymorphism rate of 16.7% (8/48), followed by GT1A1* 6 (211G > A) polymorphisms with the polymorphism rate of 4.2% (2/48). The incidences of grade 3~4 diarrhea and grade 3~4 neutropenia after Irinotecan treatment in the patients with UGT1A1 polymorphisms were 60.0% and 40.0% respectively, which were significantly higher than those of the patients with wild type UGT1A1 (21.1% and 15.8% respectively, P < 0.05). UGT1A1 polymorphism rates were 45.5% (5/11) in female patients and 13.5% (5/37) in male patients, which were significantly different (P < 0.05). ConclusionsIn EC patients, 2 polymorphism loci including UGT1A1* 93 (-3156G > A) and GT1A1* 6 (211G > A) can effectively predict adverse effects caused by Irinotecan treatment. UGT1A1 polymorphism rate of male patients is significantly lower than that of female patients.
ObjectiveTo investigate the relationship between the aldehyde dehydrogenase 2 gene (ALDH2) polymorphism and carotid intima-media thickness (IMT). MethodsFrom April 2013 to February 2014, 310 cases of carotid IMT thickening (IMT thickening group) from the physical examination center were included in the study and 280 cases of normal carotid IMT were regarded as controls. DNA was extracted from peripheral blood. ALDH2 gene polymorphism was detected by DNA microarray method. ResultsGenotype distributions had no deviation from Hardy-Weinberg equilibrium in both groups. Compared with controls, the frequency of AA/AG genotypes (67.4%, 41.1%; P<0.01) and the frequency of A allele (37.9%, 22.3%; P<0.001) of ALDH2 gene were apparently increased in the subjects of IMT thickening group. There was a significant difference in the frequency distribution of genotype and allele in ALDH2 between the two groups. The logistic analysis showed that the ALDH2 gene polymorphism was associated with the increased carotid IMT [OR=2.381, 95%CI (1.356, 4.213), P=0.004]. ConclusionThe ALDH2 gene polymorphism is correlated with the increased carotid IMT in the Han population of China Sichuan. The ALDH2 gene polymorphism may play an important role in genetic susceptibility of increased carotid IMT.
ObjectiveTo evaluate the relationship between tumor necrosis factor-α (TNF-α) gene promoter-308 G/A polymorphism and ankylosing spondylitis (AS) in Chinese population by meta-analysis. MethodsThe casecontrol studies about the correlation between TNF-α gene polymorphism and AS in Chinese population were retrieved from PubMed, EMbase, CNKI, CBM, WanFang Data and VIP database by two researchers. The retrieval time was from their establishment to December, 2015. After the paper screening, data extraction, and assessment of bias risk, the metaanalysis was conducted by Stata 12.0 software. ResultsA total of 11 case-control studies involving 1 154 AS patients and 1 458 controls were included. The results of meta-analysis showed that, for Chinese population, there was no significant association between TNF-α-308 G/A polymorphism and AS susceptibility (A vs. G: OR=0.96, 95% CI 0.63 to 1.47, P=0.86; AA vs. AG: OR=0.97, 95% CI 0.51 to 1.84, P=0.93; AA vs. GG: OR=0.92, 95% CI 0.32 to 2.61, P=0.87; AA+AG vs. GG; OR=1.04, 95% CI 0.60 to 1.80, P=0.89; AA vs. AG+GG: OR=1.03, 95% CI 0.58 to 1.82, P=0.92). ConclusionTo date, it has not found the relationship between TNF-α gene promoter-308 G/A polymorphism and AS in Chinese population. For the quantity and quality limitation of the included studies, the conclusion has to be verified by more large-scale highquality studies.