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.
Objective To observe the clinical characteristics of steroid-induced ocular hypertension (SIOH) in patients with uveitis, and explore the relationship between its clinical phenotype and gene polymorphism. Methods A retrospective case-control study. From July 2019 to December 2020, 576 patients with uveitis who were treated with glucocorticoid eye drops in Tianjin Medical University Eye Hospital were included in the study. Among them, there were 175 confirmed glucocorticoid responders (SRs) and 401 glucocorticoid non-responders (NRs). Seventy cases of SRs (age ≥18 years) using 1% prednisone acetate eye drops were selected as the experiment group and 64 cases of NRs were selected as the control group. The polymorphism of rs2523864 and rs3873352 of human leukocyte antigen complex group (HCG) 22 gene were detected by Sanger sequencing. To observe the clinical characteristics of SIOH after the use of glucocorticoid eye drops, and the correlation between rs2523864 and rs3873352 and the occurrence of SIOH. Differences among groups were compared with the Chi-square test or Fisher's exact test. The correlation between the occurrence of SIOH and the range of intraocular pressure increases after glucocorticoid use and the rs2523864 and rs3873352 loci were compared using the odds ratio (OR) and its 95% confidence interval (CI). Results SIOH occurred in 175 (30.4%, 175/576) of 576 patients. Among them, there were 96 males (54.9%, 96/175) and 79 females (45.1%, 79/175); the average age was 33.64±17.40 years. Steroid high responders (HRs) and steroid moderate responders (MRs) were 58 (33.1%, 58/175) and 117 (66.9%, 117/175) cases. The medication time for the increase in intraocular pressure in MRs that was 33 (19, 56) days, and in HRs that was 28 (14, 36) days, the difference of which was significant (Z=－1.999, P=0.046). No differences were found in daily doses of ocular hypertension induced by 1% prednisone acetate eye drops between MRs which was 4.24 (3.46, 4.66) drops/day and HRs that was 4.32 (3.84, 5.36) drops/day (Z=－1.676, P=0.094). The genotype and allele frequency distribution of the rs3873352 locus in the case group and HRs group were significantly different from those in the control group (P＜0.05). The intraocular pressure with rs3873352 GG genotype after the medication was higher than that with GC and CC genotype (Z=2.855, 2.628; P=0.013, 0.026), whereas there was no significant difference between different genotypes of rs2523864 (Z=3.580, P＞0.05). Genetic model analysis revealed the risk of SIOH in rs3873352 G allele carriers (GG+GC) was 2.048 times that of non-G allele carriers (OR=2.048, 95%CI: 1.027-4.081, P=0.041). The genotype and allele frequency of rs2523864 locus showed no significant difference between different group (P＞0.05). Conclusions After the use of glucocorticoid eye drops, HRs have an earlier increase in intraocular pressure than MRs. HCG22-rs3873352 gene polymorphism is related to the occurrence of SIOH, GG genotype increases the risk of SIOH, and G allele is a risk gene for SIOH.
Objective To investigate the relationship of p53 codon 72 polymorphism and susceptibility to gastric cancer in high incidence area of Hexi area of Gansu province. Methods The Arg/Pro polymorphism of p53 gene was detected by real-time PCR in 140 patients with gastric cancer, 110 patients with gastric precancerous lesion and 125 healthy controls; Helicobacter pylori (Hp) infection was detected by Warthin-Starry silver method． Results The Pro allele frequencies of p53 gene in gastric cancer cases (0.543) were higher than those in gastric precancerous lesion (0.482) and controls (0.472). The Pro genotype had a more than 1.846 fold increased risk of gastric cancer 〔OR=1.846; 95% 〗CI (1.006-3.387); P =0.046〕． With statistical analysis， the genotype of p53 gene was correlated with location and Laurens histological type （ P ＜ 0.05）. A significantly higher risk of gastric cancer was also seen in cases with p53 Pro genotype, food, Hp infection, positive mind factor and positive family history． Conclusion There is a b correlation between the p53 gene codon 72 Arg/Pro polymophism and susceptibility to gastric cancer in Hexi area of Gansu province and the Pro/Pro genotype may be one of the major risk factors in patients with gastric cancer.
ObjectiveTo explore the relationship between the single nucleotide polymorphisms of interleukin (IL)-23R gene and susceptibility to pulmonary tuberculosis in Southwest Chinese Han population.MethodsA total of 680 pulmonary tuberculosis patients (pulmonary tuberculosis group) and 680 healthy controls (healthy control group) diagnosed or examined between January 2014 and February 2016 were recruited from West China Hospital, Sichuan University. Improved multiplex ligation detection reaction (iMLDR) method was used to detect the polymorphism of rs1495965, rs7518660, rs7532161, rs10889677 and rs11465802 of IL-23R gene. The differences in allele frequency distribution, genotype, and genetic model of these five loci between pulmonary tuberculosis patients and healthy control were conducted by using SPSS20.0 and PLINK 1.07. Linkage disequilibrium and haplotype analysis were also carried out by Haploview 4.2.ResultsFinally, 657 pulmonary tuberculosis patients and 669 healthy controls were enrolled for further analyzed. The difference in the allele frequency distribution A (P=0.048), AA genotype (P=0.048) and additive model AA/GG (P=0.048) in rs1495965 was significant between the pulmonary tuberculosis group and healthy control group when we adjusted the gender and age. However, after correction by Bonferroni, the differences in allele frequency distribution, genotype and additive model of all these five loci between the two groups were not statistically significant (P>0.05). rs7518660, rs10889677 and rs11465802 had strong linkage disequilibrium (LD) with each other (r2>0.80); however, there was no association between haplotype GCA and tuberculosis susceptibility (P=0.343).ConclusionsThere is no association between rs1495965, rs7518660, rs7532161, rs10889677 and rs11465802 of IL-23R gene and genetic pulmonary tuberculosis susceptibility in Southwest Chinese Han population. To add loci in the coding region and analysis in different populations is necessary.
Objective To investigate the correlation between single nucleotide polymorphism (SNP) of complement factor H (CFH) gene and exudative age-related macular degeneration (AMD) susceptibility. Methods This is a retrospective case control study. 136 exudative AMD patients (AMD group) and 140 age-and sex- matched normal subjects (control group) were enrolled in this study. The peripheral blood was collected, polymorphism genotypes and frequency of CFH Y402H (rs1061170), CFH-257Cgt;T(rs3753394) and CFH IVS15 (rs1329428)were measured by polymerase chain reaction (PCR) and allele-specific restriction endonuclease digestion. The SHEsis software was performed on haplotype construction to analyze the frequency. Results There are TT, TC, CC genotypes and T, C allele in CFH Y402H (rs1061170); CC, CT, TT genotypes and C, T allele in CFH-257Cgt;T (rs3753394); AA, AG, GG genotypes and A, G allele in CFH IVS15 (rs1329428). The differences of genotypes and allele frequency between 2 groups were statistically significant (P＜0.05). The TC genotype in CFH Y402H, TT genotype in CFH-257Cgt;T (rs3753394) and GG genotype in CFH IVS15 (rs1329428) were associated with exudative AMD susceptibility (OR=4.11,2.55,3.11；P＜0.05). The T,C and G allele were the risk alleles (OR=3.14,1.72,1.79；P＜0.05). The differences of frequency between TCG, CTG and CTA haplotype were statistically significant(chi;2=10.53,6.60, 32.82；P＜0.05）. Conclusion There is correlation between SNPs of CFH gene and exudative AMD susceptibility.
ObjectiveTo investigate the associations of signal transducers and activators of transcription 6 (STAT6) gene polymorphisms with susceptibility to tuberculosis in western Chinese Han population.MethodsA total of 900 tuberculosis patients and 1 534 healthy controls of West China Hospital of Sichuan University were enrolled from January 2014 to February 2016. Improved multiplex ligation detection reaction method was used to detect four polymorphisms (rs1059513, rs73118432, rs841718, and rs10783813) of STAT6 gene. The allelic frequencies, genetic types, and different genetic models were analyzed using the chi-square test and unconditional logistic regression models to evaluate the associations of STAT6 gene with tuberculosis risk.ResultsEventually, a total of 856 cases and 1 511 health controls were recruited in our study. No significant differences were observed in allele frequencies, genotype distributions, or genetic models (additive model, dominant model and recessive model) at rs1059513, rs73118432, rs841718, and rs10783813 in STAT6 gene (P>0.05). We found a strong linkage disequilibrium among rs73118432, rs841718, and rs10783813, but there was no statistical difference in haplotype frequencies between the two groups (P>0.05).ConclusionsSTAT6 gene rs73118432, rs841718, rs10783813, and rs1059513 polymorphisms might have no associations with tuberculosis susceptibility in western Chinese Han population. Further studies with larger sample sizes are needed to comfirm these results.
Objective To explore the association between manganese superoxide dismutase (MnSOD) Val-9Ala polymorphism and breast cancer risk and to investigate the interaction with menopausal status by meta-analysis. Methods Such databases as The Cochrane Libtary (Issue1, 2010), Pubmed, CBM, CNKI and WanFang Data were searched from the date of their establishment to October, 2010, and the case-control studies of MnSOD Val-9Ala polymorphism and breast cancer risk were collected according to the inclusion and exclusion criteria. Then the quality of the included trials was assessed and meta-analysis was performed by RevMan 4.2.10 software. Results A total of 14 studies involving 17 842 patients were included. The results of meta-analyses showed no significant relation between MnSOD Val-9Ala polymorphism and the breast cancer susceptibility (Val/Ala vs. Val/Val: OR=1.04, 95%CI 0.93 to 1.17; Ala/Ala vs. Val/Val: OR=1.12, 95%CI 0.95 to 1.33; Ala/Ala vs. Val/Ala+Val/Val: OR=1.06, 95%CI 0.93 to 1.20; Val/Ala+ Ala/Ala vs. Val/Val: OR=1.06, 95%CI 0.94 to 1.10). However, in the subgroup analysis, the breast cancer risk significantly increased for premenopausal women (Val/Ala+Ala/Ala vs. Val/Val: OR=1.15, 95%CI 1.01 to1.31). Conclusion This meta-analysis suggests that the MnSOD Val-9Ala polymorphism is not significantly associated with the breast cancer susceptibility, but it may increase the risk of breast cancer in the presence of menopausal state.
ObjectiveTo investigate the relationship between the gene polymorphism of autophagy-related gene 3 (ATG3) and the development and clinical symptoms of tuberculosis in tuberculosis patients in western China.MethodsAccording to the inclusion and exclusion criteria, 476 tuberculosis patients (tuberculosis group) who were admitted to West China Hospital of Sichuan University from December 2014 to November 2015 and 475 healthy controls (healthy control group) who underwent health examination during the same period were finally included. High-throughput genotyping technology was used to detect genotypes of three single nucleotide polymorphisms (SNPs) (rs2638029, rs2638037, rs3732817) of ATG3 gene, and relevant clinical data of subjects were collected. The relationship between gene polymorphism and susceptibility to tuberculosis and clinical symptoms was analyzed by statistical methods such as χ2 test and logistic regression model.ResultsExcept for GA genotype [odds ratio (OR) =1.375, 95% confidence interval (CI) (1.048, 1.805), P=0.022] and dominant genetic model GG+GA [OR=1.326, 95%CI (1.024, 1.717), P=0.032] in rs2638037, there was no statistically significant difference in the allele frequency, genotype and genetic patterns of rs2638029, rs3732817 and rs2638037 between the two groups (P>0.05), after the adjustment of the gender and age. But after correction by Bonferroni, GA genotype and dominant genetic patterns GG+GA showed no statistical significance between the two groups (P=0.132, 0.201). Haplotype CGA was associated with tuberculosis susceptibility [OR=1.262, 95%CI (1.001,1.593), P=0.048]. There was a statistically significant difference in weight loss symptoms among rs2638037 genotypes (χ2=8.131, P=0.017).ConclusionsThe haplotype CGA of three SNPs of ATG3 gene may be involved in the development of tuberculosis. The rs2638037 single nucleotide polymorphism may be related to weight loss, and more research is needed in the future.
Objective To analyze the human leukocyte antigen (HLA) gene polymorphism and haplotype frequency and distribution in Han patients with end stage renal disease (ESRD) in Sichuan province, and explore the correlation of HLA gene polymorphism and haplotype with the susceptibility to ESRD in Sichuan Han patients. Methods Polymerase chain reaction-sequence specific oligonucleotide probe hybridization typing technique was used to detect the HLA-A, -B, -DRB1, and -DQB1 genotypes of Han patients with ESRD and healthy participants. The allele and haplotype frequencies in the ESRD group and the control group were analyzed using SPSS 25.0 and Arlequin 3.5.2.2 softwares. Results A total of 756 ESRD patients and 1118 healthy participants were enrolled. In the four loci of HLA-A, -B, -DRB1, and -DQB1, the frequency of HLA-B*39 allele in the ESRD group was higher than that in the control group [3.37% vs. 2.19%; χ2=4.850, P=0.028, odds ratio (OR)=1.558, 95% confidence interval (CI) (1.047, 2.319)], the frequency of HLA-DQB1*06 allele in the ESRD group was lower than that in the control group [17.39% vs. 21.20%; χ2=8.264, P=0.004, OR=0.783, 95%CI (0.662, 0.925)], and the frequency of HLA-DQB1*04 allele in the ESRD group was higher than that in the control group [7.41% vs. 5.46%; χ2=5.867, P=0.015, OR=1.386, 95%CI (1.063, 1.807)]. The frequencies of 10 haplotypes, including HLA-A*11-B*39, HLA-DRB1*15-DQB1*06, and HLA-DRB1*04-DQB1*04, were significantly different between the ESRD group and the control group (P<0.05), among which 9 haplotypes were possibly susceptible to ESRD and 1 haplotype was possibly protective. Conclusions HLA gene polymorphism is closely related to the susceptibility to ESRD. HLA-B*39 and HLA-DQB1*04 may be susceptible genes for ESRD in Sichuan Han patients, while HLA-DQB1*06 may be a protective gene. In addition, 10 HLA haplotypes are possibly associated with the susceptibility to ESRD in Sichuan Han patients.