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.
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.
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.
Objective To detect the single nucleotide polymorphisms ( SNPs) in the upstream promoter region of chemokine like factor ( CKLF) gene and analyze their possible associations with asthma and asthma-related phenotypes. Methods Direct Sequence of the 1553bp upstream promoter region of CKLF gene was performed in 245 Chinese Han human genomic DNAs ( 119 asthmatics and 126 controls) .The frequencies of alleles, genotypes, and haplotypes were determined and the association of these SNPs with asthma were further analyzed. Results Four novel SNPs, SNP88 ( T gt; C) , SNP196 ( T gt; C) , SNP568 ( C gt;G) , and SNP1047 ( C gt; G) were found in the promoter region of CKLF. The frequency of rare allele was 0. 168 ( SNP88C) , 0. 168 ( SNP196C) , 0. 352 ( SNP568G) and 0. 167 ( SNP1047G) , respectively.Haplotypes, their frequencies and the linkage disequilibrium coefficients between SNPs were constructed.Complete linkage disequilibrium( LDs) were observed between SNP88 and SNP196, SNP88 and SNP1047,as well as SNP196 and SNP1047, respectively ( D′=1. 000, r2 = 1. 000) . SNP568 was in partial LD with the other three SNPs ( r2 = 0. 366) . No association between asthma and the SNPs was observed. Conclusions Four SNPs in the regulatory region of CKLF in Chinese Han population were firstly identified. Although no significant correlation with asthma was revealed, the SNP and haplotype information is useful for other disease association studies in the future.
ObjectiveTo investigate the relationship between single nucleotide polymorphisms (SNP) in the CHRM1 gene and genetic susceptibility to high myopia (HM) in the Han population of Henan Province. MethodsA retrospective case-control study. From January 2021 to April 2023, 576 HM patients (HM group) and 768 healthy volunteers (control group) were recruited from the Department of Ophthalmology, the First Affiliated Hospital of Zhengzhou University. All participants were of Han ethnicity from Henan Province. SNP data for the CHRM1 gene in the Northern Han Chinese population were downloaded from the 1000 Genomes Project Online Website, with screening criteria of Hardy-Weinberg equilibrium P＞0.05 and minor allele frequency＞0.05. Haploview software was used to analyze HapMap genotypes, identifying 5 tagSNP: rs55885673, rs544978, rs56995061, rs1942499, and rs2075748. MassARRAY system was employed for genotyping the 5 tagSNP loci. The SHEsis online software was employed to analyze the distribution differences of genotypes and allele frequencies between the two groups. Linkage disequilibrium coefficient D' was used to evaluate the recombination events between SNP loci, and haplotypes with frequencies exceeding 3% were constructed for statistical analysis. Results The age of the HM group was significantly lower than that of the control group (t=18.515, P＜0.05), while no significant difference was observed in gender distribution (χ2=2.869, P=0.087). Compared with the control group, the HM group showed significantly higher frequencies of the C allele [odds ratio (OR)=1.44, 95% confidence interval (CI): 1.09-1.91, Pc=0.045)] and CC genotype (OR=1.50, 95%CI: 1.11-2.02, Pc=0.038) at the rs56995061 locus, and significantly lower frequencies of the T allele (OR=0.69, 95%CI: 0.52-0.91, Pc=0.045) and CT genotype (OR=0.67, 95%CI: 0.49-0.91, Pc=0.045). Additionally, the CT genotype frequency at the rs2075748 locus was significantly lower in the HM group (OR=0.66, 95%CI: 0.53-0.84, Pc=0.002). The haplotype G-T-A-A formed by rs55885673-rs56995061-rs1942499-rs544978 was significantly less frequent in the HM group (OR=0.71, 95%CI: 0.54-0.94, P=0.170).ConclusionsThe polymorphisms at the SNP loci rs56995061 and rs2075748 in the CHRM1 gene are associated with the genetic susceptibility to high myopia in the Chinese Han population. The G-T-A-A haplotype composed of rs55885673-rs56995061-rs1942499-rs544978 reduces the susceptibility to high myopia.
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.
【Abstract】 Objective To analyze the correlations between the mt5351G and mt6680C genotypes in mitochondrial DNA ( mtDNA) haplogroup M and susceptibility to high altitude pulmonary edema ( HAPE)among the Hans. Methods Specimens from206 Hans cases of HAPE and 144 matched Hans controls were collected. Then PCR-RFLP method was used to determine haplogroup M and N of mtDNA, and PCR-LDR was used to genotype mt5351G and mt6680C in the haplogroup M in these samples. Results The frequencies of haplogroup Mand N were 49. 0% and 51.0% in the HAPE patients, and 47. 2% and 52. 8% in the controls, respectively, with no significant difference between the HAPE patients and the controls. In the haplogroup M, the genotype of mt6680C and mt5351G frequencies in the HAPE patients were both significantly higher than the controls ( both 12. 0% vs. 1. 5% , P = 0. 016) . Conclusion The existence of mt5351G and mt6680C genotypes in the haplogroup Mis a risk factor for HAPE among the Hans.