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.
ObjectiveTo introduce transforming growth factor β(TGFβ) and the relationship between TGFβ and graft rejection. Methods Relevent articles in recent years were reviewed.ResultsThe immunodepressive function of TGFβ could resist transplant organ rejection injury in early postoperative period ; meanwhile TGFβ also caused fibroblast migration and promoted matrix deposition by increasing collagen production and decreasing collagen breakdown via inhibition of collagenases,which resulted in transplant organ fibrosis and arteriosclerosis, gene polymorphisms of the TGFβ were associated with it. Moreover,ischemia reperfusion injury and immunodepressive drug also affected production of TGFβ.ConclusionTGFβ as a pleiotropic and multifunctional cytokine contributes to the development of acute and chronic rejection.
Objective To evaluate the correlation of TNF-α G308A polymorphism and rheumatic heart disease (RHD) using meta-analysis. Methods Databases including PubMed, EMbase, CNKI and WanFang Data were searched to collect case-control study on the correlation of TNF-α G308A polymorphism and RHD, published from January 1990 to June 2011. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the methodological quality of the included studies. Then meta-analysis was performed using RevMan 5.1 and SPSS 16.0. Results A total of 5 studies were included, involving 539 RHD cases and 624 controls. The results of meta-analysis according to recessive genetic model of TNF-α G308A showed that there were significant differences in RHD risk between the AA genotype carriers and the GA+GG genotype carries (OR=5.06, 95%CI 2.15 to 11.89, P=0.0002), the same as the results of meta-analysis calculated according to dominant genetic model (OR=3.14, 95%CI 1.05 to 9.38, P=0.04). Conclusion Current evidence shows that TNF-α G308A polymorphism is related to RHD, and the AA genotype carriers tend to face an increasing RHD risk. This conclusion still needs to be further proved by more high-quality and large-scale clinical trials.
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.
ObjectiveTo review the recent progress in research on the role of estrogen and estrogen receptor on the onset and progression of adolescent idiopathic scoliosis (AIS). MethodsThe recently published clinical and experimental 1iterature at home and abroad on abnormality of estrogen and its receptor in AIS was reviewed and summarized. ResultsThere are many abnormal changes of estrogen and estrogen receptor in most AIS patients, including higher serum estrogen concentration, unusual cellular response to estrogen, late age at menarche, and gene polymorphisms of estrogen receptor, which are closely associated with AIS predisposition, curve severity, and scoliosis progression. ConclusionEstrogen and its receptor participate in the onset and progression of AIS by certain mechanisms, but exact mechanism remains indefinite, which needs further research to better define the role of estrogen and its receptor in AIS.
ObjectiveTo investigate the role of leptin receptor gene Gln223Arg polymorphism in pathogenesis of asthma. MethodsOne hundred and eighty-five asthmatic outpatients and inpatients in the Qingdao Municipal Hospital between June 2009 and May 2012 were recruited in the study.Two hundred and seven healthy volunteers were recruited as control.Peripheral blood was sampled from all subjects for measuring serum leptin level by ELISA,and analyzing leptin receptor gene Gln223Arg genotypes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) in white blood cells. ResultsThere was significant difference in frequency distribution of leptin receptor gene Gln223Arg genotype between the asthma group and the health group (χ2=6.173,P=0.013,OR=1.697,95%CI 1.115-2.585).The GG genotype was associated with a 1.895-fold increased risk for asthma than the GA+AA genotype (χ2=7.283,P=0.007,OR=1.895,95%CI 1.187-3.024).The serum leptin level of the GG genotype group was significantly higher than that in the GA+AA genotype group[(2.56±1.47) ng/mL vs.(2.16±1.66) ng/mL]. ConclusionLeptin receptor gene Gln223Arg polymorphism is correlated with asthma, and the G allele might be the genetic factor that contributes to individual susceptibility for asthma by causing high serum leptin level.
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.
Objective To investigate the relationship between cyclooxygenase-2 (COX-2) gene polymorphism and genetic susceptibility to esophageal cancer. Methods The PubMed and EMbase databases were searched from the date of their establishment to January 1st, 2011 to collect the case-control studies on COX-2 polymorphism and susceptibility to esophageal cancer. For the population genotype distributions of both esophagus cancer group and control group, their odds ratios (ORs) and 95% confidence intervals (CIs) were taken as the effect indexes, either the fixed or random effect model was applied to conducted Meta-analysis in homozygote comparison, dominant and recessive genetic models, and the publication bias was assessed then. All statistical analyses were conducted with Stata11.0 software. Results A total of five case-control studies were included. The results of meta-analyses showed for the COX-2-765Ggt;C polymorphism, the CC+GC genotype was associated with the risk of esophageal cancer in a dominant genetic model (CC+GC vs. GG: OR=1.806, 95% CI 1.050 to 3.106); for the COX-2-1195Ggt;A polymorphism, the AA genotype was associated with the risk of esophageal cancer in homozygote comparison and recessive genetic models, the AA+GA genotype was associated with the risk of esophageal cancer in a dominant genetic model. Conclusion It is suggested that COX-2 polymorphism may be associated with genetic susceptibility to esophageal cancer.
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.