Tuberculosis remains a major public health problem. Genetic epidemiological studies have shown that the differences in host genes partly determine the susceptibility to tuberculosis. The occurrence of tuberculosis is the result of the joint action of Mycobacterium tuberculosis and host gene regulation immune response. The study of susceptibility candidate genes has differences in race, population and region, and the study of susceptibility gene polymorphism still has a long way to go in clinical precision diagnosis and treatment. The study and clinical application of mendelian susceptibility to mycobacterial disease can be used as a classic application of precision medical treatment in tuberculosis; although it is a rare case, this model is worthy of reference.
Warfarin is one of the most frequently prescribed oral anticoagulant. Many researches have shown that the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex 1 (VKORC1) genotypes have been strongly associated with warfarin maintenance doses. Warfarin maintenance doses can be accurately predicted by use of dosing algorithms including genetic and clinical information. Although several clinical trials demonstrated mixed results, calling into question the utility of this approach. The present data do not support genetic testing to guide warfarin maintenance doses, but in the setting where genotype data are available, use of this approach is reasonable. Ongoing trials are expected to provide more data, and more work is needed to define dosing algorithms that include appropriate variables in minority populations. All these work will further improve the clinical application of genotype-guided warfarin maintenance doses.
ObjectiveTo investigate the relationship between the polymorphisms of estrogen receptor α (ERα) gene PvuⅡ, XbaⅠ and breast hyperplasia. MethodsPolymerase chain reaction-restriction fragment length polymorphism was used to detect the polymorphisms of ERα gene PvuⅡ, XbaⅠ in breast hyperplasia patients (study group, n=89) and healthy controls (control group, n=35). ResultsThe differences of the genotypic frequency and allele frequency of the ERα gene Xba Ⅰ were significant between the study group and the control group (Plt;0.05). According to analysis of the odds ratio (OR), the risk of developing breast hyperplasia for X allele carriers was 0.551 as compared with x allele carriers. But there was no significant difference for the gene polymorphism of PvuⅡ between the study group and the control group (Pgt;0.05). ConclusionThe polymorphisms of XbaⅠof ERα gene is associated with breast hyperplasia and the mutant gene increases breast hyperplasia risk.
Abstract： Objective To explore the association between transforming growth factor-β receptor typeⅡ (TGFBR2) gene rs6785358 and rs764522 polymorphisms and rheumatic heart disease (RHD) in Chinese Han People. Methods The research design was a case-control study. A total of 207 patients who were hospitalized in Nanjing First Hospital Affiliated to Nanjing Medical University between October 2008 and January 2011 with RHD served as RHD group while 225 age and gender matched healthy adults as control group. Polymerase chain reaction-restriction length polymorphism (PCR-RFLP) technique was used to determine TGFBR2 gene rs6785358 and rs764522 polymorphisms. Results The frequencies of genotype AA, AG and GG of rs6785358 in RHD group and control group were 72.0%, 25.1%, 2.9% and 68.9％, 28.0％, 3.1％,respectively. There was no significant difference in the distribution of genotype frequencies for rs6785358 between RHD group and control group（χ2=0.50，P=0.78）. The frequencies of allele A and G of rs6785358 in RHD group and control group were 84.5％, 15.5％ and 82.9％, 17.1％,respectively. There was no significant difference in the distribution of allele frequencies for rs6785358 between RHD group and control group（χ2=0.43，P=0.51）. The frequencies of genotype CC, CG and GG of rs764522 in RHD group and control group were 77.3%, 21.3%, 1.4% and 75.6％, 21.3％, 3.1％, respectively. There was no significant difference in the distribution of genotype frequencies for rs764522 between RHD group and control group（χ2=1.33，P=0.51）. The frequencies of allele C and G of rs764522 in RHD group and control group were 87.9％, 12.1％ and 86.2％, 13.8％,respectively. There was no significant difference in the distribution of allele frequencies for rs764522 between RHD group and control group（χ2=0.55，P=0.46）. Further analysis by sex stratification showed that no statistical significance was detected in the distribution of genotype and allele frequencies for rs6785358 or rs764522 between RHD patients and controls. Conclusion TGFBR2 gene rs6785358 and rs764522 polymorphisms are not associated with RHD in Chinese Han people.
ObjectiveTo investigate the association between tumor necrosis factor (TNF)-α gene polymorphism and susceptibility to chronic obstructive pulmonary disease (COPD) in eastern Heilongjiang province.MethodsA total of 347 COPD patients in the Department of Respiratory Medicine, the First Affiliated Hospital of Jiamusi University, were enrolled from January 2016 to January 2017. In the same period, 338 healthy subjects in the hospital physical examination center were selected as controls. The genotype of the two groups was analyzed by high resolution melting (HRM) and gene sequencing. The genotype and allele probability of the two groups were compared and analyzed by the SHEsis genetic imbalance haplotype analysis.ResultsBoth TNF-a –308 G/A co-dominant model and recessive model have significant differences between COPD patients and healthy subjects (P=0.036, OR 1.512, 95%CI 1.023 – 2.234; P=0.027, OR 1.202, 95%CI 1.024 – 1.741). –850G/A co-dominant model (P=0.000, OR 1.781, 95%CI 1.363 – 2.329), dominant model (P=0.000, OR 0.391 7, 95%CI 1.363 – 2.329) and hyper-dominant model (P=0.000, OR 2.680, 95%CI 1.728 – 4.156) in the two groups were statistically different. The haploid analysis and haploid genotype analysis showed statistically significant differences (all P<0.05, OR>1, 95%CI>1) at +489, –308, –850 sites by allele A, G, A, respectively between the two groups. There was a significant difference in the lung function between the –308G/A, –863C/A mutant genome and the wild type (P=0.038, P=0.02) in COPD patients according to the classification of lung function.ConclusionsA allele in TNF-α –308 and G allele in TNF-α –850 locus may be risk factors for COPD in the eastern Heilongjiang Province, and the risk of homozygous genotype is higher. +489A, –308G and –850A respectively may be the predisposing factor of COPD while the three genotypes of AGA patients were at higher risk. TNF-α –308 A allele and –863 A allele are related to lung function deterioration, and the two sites with A allele in patients with COPD indicate poor lung function.
ObjectiveTo investigate the correlation between TLR5 rs5744174 gene polymorphism and Streptococcus pneumoniae pneumonia.MethodsOne-hundred and six patients with Streptococcus pneumoniae pneumonia admitted to this hospital from January 2014 to October 2018 were selected as an observation group, and 85 healthy subjects were selected as a control group during the same period. The clinical and pathological data of the subjects were collected, polymorphism of TLR5 rs5744174 gene was analyzed by PCR and sequencing, and the relationships between cell classification count, C-reactive protein (CRP) level in bronchoalveolar lavage fluid (BALF) and TLR5 rs5744174 gene polymorphism in the patients with Streptococcus pneumoniae pneumonia were analyzed.ResultsThere were significant differences in age, smoking, alcoholism, diabetes and the other general data between the observation group and the control group (P<0.05). The distribution of TLR5 rs5744174 genotype in the observation group and the control group was in accordance with Hardy-Weinberg equilibrium test level (χ2=16.89 for the observation group, χ2=10.76 for the control group, both P>0.05). There was no significant difference in the distribution frequency of TLR5 rs5744174 (C < T) genotype and allele between the two groups (P>0.05). There were significant differences in the proportion of diabetes mellitus among the three genotypes (CC, CT, TT) of the patients with Streptococcus pneumoniae pneumonia (P<0.05). The percentage of neutrophils and CRP levels in BALF were significantly different (P<0.05).ConclusionThe polymorphism of TLR5 rs5744174 gene may not be related to the occurrence of Streptococcus pneumoniae pneumonia, but is related to the proportion of complicated diabetes mellitus, the percentage of neutrophils and the level of CRP in patients with Streptococcus pneumoniae pneumonia, which may affect the degree of inflammation.
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.
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 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.
Objective To evaluate the association between N-acetyltransferase 2 (NAT2) gene polymorphisms and the risk of antituberculosis drug-induced liver injury (ATDILI). Methods We searched the PubMed, Embase, Wanfang, China National Knowledge Internet and VIP databases to find case-control studies, with the last updated search being performed on June 2017. Odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the strength of association. Results A total of 29 studies, involving 1 382 cases and 5 967 controls were included. The results of the Meta-analysis indicated that NAT2 slow acetylators were associated with increased risk of ATDILI compared with fast and intermediate acetylators [OR=3.08, 95%CI (2.44, 3.88), P<0.000 01]. Similar results were also found in subgroup analysis when stratified by ethnicity, isoniazid dosage and diagnostic criteria of ATDILI. Conclusion Individuals with NAT2 slow acetylators may have increased risk of ATDILI.