Objective To investigate whether ADAM33 ( A disintegrin and metalloproteinase 33) gene polymorphismhas effect on the airway inflammation of COPD. Methods A total of 312 COPD patients were recruited for this study. Four polymorphic loci ( T2, T1, S2, and Q-1) of ADAM33 were selected for genotyping by using the polymerase chain reaction-restriction fragment length polymorphism ( PCR-RFLP) method. Total and differential cell counts, contents of TNF-α, IL-6, IL-8, and VEGF in induced sputumwere detected. The relationship between genotypes and inflammatory reaction was analyzed. Results On locus T2, the cell counts and content of TNF-αin induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.01 and Plt;0.05) . On locus T1, the lymphocyte counts in induced sputumincreased significantly in the carriers with GG genotype than those with AA and AG genotypes ( Plt;0.05) ; but the content of IL-8 in induced sputumwas higher in AA and AG genotypes ( Plt;0.05) . On locus Q-1, the contents of VEGF and IL-8 in induced sputum increased significantly in the carriers with GG genotype than those with AA and AG genotypes (Plt;0.05) . On locus S2, the total cell counts in induced sputumincreased significantly in the carriers with GG genotype than those with CC and CG genotypes ( Plt;0.05) , and the content of IL-8 in induced sputum increased significantly in GG genotype ( Plt;0.01 ) . Conclusion These results suggest that ADAM33 polymorphism may participate the pathogenesis of COPD by promoting airway inflammation.
Objective To reveal the association between the single nucleotide polymorphism (SNP) of v-maf musculoaponeurotic fibrosarcoma oncogene homolog B (MAFB) gene rs17820943 locus and non-syndromic cleft l ip with or without cleft palate (NSCL/P) in the southern Chinese Han population. Methods Genotyping of MAFB gene rs17820943 polymorphism was carried out in 300 patients with NSCL/P, 354 normal controls, and an additional 168 case-parent trios with matrix-assisted laser desorption/ionisation time-of-fl ight (MALDI-TOF) mass spectrometry. Then based on the genotypingresults, both a case-control association study and a case-parent trio association study were performed. Results Significant differences were found in the allele and genotype frequencies of rs17820943 locus between case and control groups (Pallele=0.001 and Pgenotype=0.002, respectively). To be specific, the odds radio (OR) values and 95% confidence interval (95%CI) of allele T (frequencies of cases ∶ controls = 0.358 ∶ 0.448) and genotype TT (frequencies of cases ∶ controls = 0.110 ∶ 0.195) were ORT = 0.69 (95%CI: 0.55-0.86) and ORTT = 0.43 (95%CI: 0.26-0.70), respectively. Subsequent case-parent trio analysis also indicated an association between MAFB rs17820943 variant and the risk of NSCL/P (ORT vs. C = 0.55, 95%CI: 0.41-0.75, P value of transmission disequilibrium test was 0.000). Conclusion Polymorphism of MAFB gene rs17820943 locus is associated with NSCL/P in the southern Chinese Han population; MAFB rs17820943 variant may be a susceptible gene of NSCL/P.
Objective To explore the relationships between the polymorphisms of inhibitor genes WIF1 and DKK1 in WNT signaling pathway and susceptibility to tuberculosis, clinical characteristics and laboratory indexes. Methods From December 2014 to November 2016, 475 tuberculosis patients and 370 healthy controls of West China Hospital of Sichuan University were enrolled in the study, and the clinical data of the subjects were collected. High-throughput genotyping technique was used to detect the polymorphisms of WIF1 rs58635985 and DKK1 rs11001548 in WNT signaling pathway. The allele frequency distribution, genotype, genetic model, clinical features and laboratory indexes of two single nucleotide polymorphisms were analyzed by χ2 test and logistic regression analysis. Results There was no significant difference in the allele frequency distribution (P=0.275, 0.949), genotype (P=0.214, 0.659) or genetic models: additive model (P=0.214, 0.659), dominant model (P=0.414, 0.827), recessive model (P=0.227, 0.658) of rs58635985 and rs11001548 between the tuberculosis group and the healthy control group. Subgroup analysis showed no significant difference in allele and genotype distribution between rs58635985 and rs11001548 (pulmonary tuberculosis group vs. healthy control group: P>0.05; pulmonary tuberculosis groupvs. extra-pulmonary tuberculosis group: P>0.05). There was no significant difference in the clinical features (fever, night sweat, fatigue,etc.) or laboratory indexes (complete blood count, erythrocyte sedimentation rate, TB-DNA, etc.) (P>0.05). Conclusions There is no association between rs58635985 of WIF1 gene or rs11001548 of DKK1 gene and genetic susceptibility, clinical characteristics and laboratory indexes in Han population in Western China. To expand the sample size for verification and analysis in different populations is necessary.
Objective To explore the correlation between the single nucleotide polymorphism (SNP) in the promotor of hepatic l ipase (HL) gene and untraumatic avascular necrosis of the femoral head (ANFH). Methods Between January 2007 and June 2009, 243 patients with ANFH were treated (case group), including 143 cases of steroid-induced, 79 cases of alchol-induced, and 21 cases of idiopathic. There were 156 males and 87 females with an age ranged from 16 to 64 years. Atotal of 96 normal individuals (matched for age, sex, and nation) served as control group. The blood sample of all subjects were collected to extract DNA. The promotor of HL was sequenced to find the SNP. A statistic on the frequencies of the genotype and the allele of the SNP was made. The frequencies of the genotype and the allele were analyzed with χ2 test according to case-control principle. Results The rs59644784 and rs1800588 were found in the sequenced region. It was accorded with Hardy-Weinbery genetic equil ibrium law in rs59644784 and rs1800588 of the control group and case group. There was no significant difference in the allele and genotype of rs59644784 and rs1800588 between the control group and case group (P gt; 0.05). The two SNPs existed complete l inkage disequil ibrium according to the l inkage disequil ibrium analysis. Conclusion The heterozygosity of the SNP is not consistency, and heterozygosity may be associated with the diversity of the race. ANFH is not associated with rs59644784 and rs1800588 SNPs.
ObjectiveTo explore the relationship between hexokinase domain-containing protein 1 (HKDC-1) single nucleotide polymorphism (SNP) and first-line anti-tuberculosis drug-induced liver injury (ATDILI) in tuberculosis patients in western China.MethodsFrom November 2016 to April 2018, 746 tuberculosis patients treated in West China Hospital of Sichuan University were collected and divided into ATDILI group and non-ATDILI group according to the liver function indicators. DNA was extracted by QIAamp® DNA Blood Mini Kit (Qiagen, Germany). Seven SNPs of the HKDC-1 gene were genotyped by high-throughput genotyping technique and the differences between the two groups were compared.ResultsThere were 118 ATDILI and 628 non-ATDILI cases enrolled in this study. In clinical symptoms, the differences in incidences of fever and weight loss between the two groups were statistically significant (P=0.004, 0.024). The C allele at rs906219 was associated with low susceptibility to ATDILI [odds ratio (OR)=0.737, 95% confidence interval (CI) (0.556, 0.957), P=0.033], and the additive model and dominant model showed that CC/CA genotype had a lower risk of ATDILI than AA genotype [CC vs. AA: OR=0.563, 95%CI (0.325, 0.976), P=0.039; CC+CA vs. AA: OR=0.533, 95%CI (0.348, 0.817), P=0.004].ConclusionThe SNP of rs906219 in HKDC-1 is correlated with ATDILI occurrence in tuberculosis patients in western China, which provides clues for personalized anti-tuberculosis treatment.
Objective To review the research progress of bone morphogenetic protein (BMP) and the liability of ossification of the posterior longitudinal ligament (OPLL). Methods Recent literature concerning BMP and the liability of OPLL was reviewed, analysed, and summarized. Results The single nucleotide polymorphisms (SNPs) of BMP gene may produce a minor cumulative effect and increase individual susceptibility to OPLL. A variety of environmental factors can promote the occurrence and development of OPLL by increasing the expression of BMP gene. Conclusion The SNPs of BMP gene may increase individual susceptibility to OPLL. However, interaction of cumulative effect of the SNPs and environmental factors can promote the liability to OPLL.
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 whether interleukin-10 ( IL-10 ) gene single nucleotide polymorphisms are associated with asthma. Methods The frequency of three single nucleotide polymorphisms ( rs1800896, rs3024492, and rs3024496) and haplotypes of IL-10 gene were analysed in 302 adult asthmatic subjects and 275 controls of Han Chinese in Guangzhou using MALDI-TOF-MS and MassARRAY-IPLEX. The genotype and allele frequencies were analyzed by Chi-square test in both groups.Logistic regression analysis with adjustment for age and sex was conducted. Odds ratio ( OR) and 95%confidence interval ( 95% CI) were calculated to analyze the associations between the susceptibility of asthma and genotypes. Results ①Three genotypes GG, GA, and AA of rs1800896 were found in Han Chinese inGuangzhou. The frequencies of GG, GA, and AA genotypes were 2. 12% , 39. 65% , and 58. 23% ,respectively. The relative risk of developing asthma in the carriers of GA was significantly higher than that in the carriers of AA ( OR=4. 827, P lt;0. 001) . ②Two genotypes AA and AT of rs3024492 were found in Han Chinese in Guangzhou. The frequencies of AA and AT genotypes were 1. 22% and 98. 78% , respectively.The rs3024492 polymorphism was not related to susceptibility in asthma. ③Two genotypes TT and CT of rs3024496 were found in Han Chinese in Guangzhou. The frequencies of TT and CT genotypes were 90. 59% and 9. 41% , respectively. The rs3024496 polymorphism was not related to susceptibility in asthma. Conclusion In IL-10 gene single nucleotide polymorphisms, rs1800896 but not rs3024492 and rs3024496 isstatistically related with the development of asthma.
ObjectiveTo investigate the association between single nucleotide polymorphism (SNP) rs3754219 in the glucose transporters 1 (GLUT1) gene and genetic susceptibility to type 2 diabetes mellitus (T2DM) in Han population in Guangdong Province.MethodsA total of 1 092 T2DM patients (case group) and 1 092 healthy controls (control group) diagnosed or examined between November 2011 and October 2014 form 10 hospitals were enrolled in this study. SNPscanTM SNP classification technology was used to detect the polymorphism of rs3754219 of GLUT1 genetype. Finally, 1 067 T2DM patients and 1 054 healthy controls were included, removing 37 individuals with SNP typing deletion rates >20% and 26 individucals with failed SNP site genotyping. The differences in allele frequency distribution, genotype, and genetic models between the two groups were analyzed.ResultsAfter correction for age and body mass index, there was no statistically significant difference in allele frequency or polymorphism genotype frequency of rs3754219 (P>0.05). There was no statistically significant difference between the two groups under different genetic models (P>0.05).ConclusionGenetic susceptibility to T2DM in Han population in Guangdong Province may be unrelated to the GLUT1 rs3754219 SNP.
ObjectiveTo understand the genetics associations between low-density lipoprotein receptor-related protein 5 (LRP5) gene polymorphisms and susceptibility of osteoporosis in patients with chronic obstructive pulmonary disease (COPD).MethodsThree hundred and seventy-nine patients with acute exacerbation of COPD were divided into groups of non osteoporosis and osteoporosis. Genomic DNA was extracted from all patients. UCSC genome browser and Haploview 4.2 software were used to screen tag single nucleotide polymorphisms (tagSNP) of LRP5 gene. The tagSNP was genotyped by Sequenom MassARRAY SNP detection method. Logistic regression were used to analysis the odds ratio (OR) values and confidence intervals (CI) of each SNP in different genetic models to assess the association between single nucleotide polymorphisms in LRP5 gene and osteoporosis in COPD patients.ResultsEight tagSNPs of LRP5 gene (rs312016 T/C, rs312017 C/T, rs312018 A/G, rs3736228 C/T, rs901823 T/C, rs589963 G/A, rs638051 A/G, rs671494 C/A) were selected for association analysis. Patients of rs901823 carrying C/C genotype had a higher risk of osteoporosis than those carrying T/T and C/T genotypes in COPD patients (in recessive mode, C/C vs. T/T+C/T, OR=9.42, 95%CI=2.01–44.29), P=0.000 431 8).ConclusionsThere is a significant association between rs901823 of LRP5 gene and osteoporosis in patients with COPD. Further studies are needed to discover the mechanism of LRP5 gene polymorphism in the pathogenesis of osteoporosis in COPD patients.