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Arsenic is a kind of non-metallic substance with carcinogenic effect, which widely exists in the natural environment. Chronic arsenic exposure will cause a series of health damage involving multiple organs of the whole body. Because of its unclear pathogenesis, lack of specific drugs and early biomarkers, it has become the focus and hotspot of scientific and technological workers for a long time. Epigenetic modification not only correlates with arsenic exposure, but also participates in early arsenic-induced damage by regulating the expression of key molecules, which has become an important research direction of arsenic exposure mechanism. As one of the important modes of epigenetic modification, DNA methylation is expected to provide a new therapeutic target for endemic arsenism. However, how DNA methylation regulates the expression of key genes induced by arsenic and participates in the occurrence and development of arsenism and its relationship with the mechanism of arsenism need to be further studied. The research progress of DNA methylation in the pathogenesis of arsenism is reviewed.
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Objective:To investigate the genetic correlation of interleukin-12 (IL-12) pathway-related gene single nucleotide polymorphisms (SNPs) with psoriasis vulgaris and their interaction with HLA-Cw*0602 in populations of Mongolian and Han nationalities in Inner Mongolia.Methods:From December 2012 to March 2018, 1 409 inpatients with psoriasis vulgaris (1 030 of Han nationality and 379 of Mongo-lian nationality) and 1 483 healthy controls (965 of Han nationality and 518 of Mongolian nationality) were collected from the Affiliated Hospital of Inner Mongolia Medical University, and served as patient group and control group respectively. Five milliliters of peripheral venous blood samples were collected from these subjects, and DNA was extracted. Nine SNPs located in the coding regions of IL-12 pathway-related genes were selected, including IL-12B (rs2082412, rs2288831, rs3212227, rs3213094, rs7709212) , IL-23R (rs11209026, rs2201841, rs7530511) and IL-28RA (rs4649203) genes, and detected by next-generation sequencing. HLA-Cw*0602 was genotyped by polymerase chain reaction with sequence-specific primers (PCR-SSP) . Statistical analysis was carried out with PLINK1.07 software, Chi-square test was used to compare allele frequencies between the 2 groups, relative risk estimates of alleles were calculated by using odds ratio ( OR) , and chi-square test for R × C contingency tables was used for haplotype analysis. Results:The allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in the patients with psoriasis vulgaris of Han nationality than in the controls of Han nationality (all P < 0.005) ; the allele frequency of rs3213094 in the IL-12B gene was significantly lower in the patients of Mongolian nationality than in the controls of Mongolian nationality ( P < 0.005) . The prevalence of HLA-Cw*0602 was significantly lower in the patients with psoriasis vulgaris of Han and Mongolian nationalities than in the controls of corresponding nationalities (both P < 0.005) . As stratification analysis showed, the allele frequencies of rs2082412, rs2288831, rs3212227, rs3213094 and rs7709212 in the IL-12B gene were significantly lower in HLA-Cw*0602-positive patients of Han nationality than in HLA-Cw*0602-positive controls of Han nationality (all P < 0.005) , while there was no significant difference between HLA-Cw*0602-negative patients of Han nationality and HLA-Cw*0602-negative controls of Han nationality (all P > 0.05) . Among the HLA-Cw*0602-positive or negative populations of Mongolian nationality, no significant difference was observed in the allele frequencies between the patients and controls (all P > 0.005) . Haplotypes were constructed using 5 SNPs in the IL-12B gene, and there was no significant difference in the frequencies of 6 haplotypes between the patients and controls of Mongolian or Han nationality (all P > 0.005) ; stratification analysis showed that there was no significant difference in the frequencies of 7 haplotypes between HLA-Cw*0602-positive/negative patients and controls of Mongolian or Han nationality (all P > 0.005) . Conclusion:IL-12 pathway-related gene polymorphisms are associated with psoriasis vulgaris in the populations of Mongolian and Han nationalities in Inner Mongolia, and there may be interaction between IL-12B and HLA-Cw*0602 in the occurrence of psoriasis vulgaris.
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Objective:To evaluate the effect of ribosomal protein L34 (RPL34) gene knockdown on the proliferation and apoptosis of human cutaneous squamous cell carcinoma (cSCC) cells.Methods:From January 2016 to January 2017, 14 paraffin-embedded skin samples of cSCC and 16 paraffin-embedded normal skin tissue samples were collected from Department of Dermatology and Venereology, the Affiliated Hospital of Inner Mongolia Medical University, and RPL34 expression in the skin tissues was analyzed by immunohistochemical study. A lentivirus vector containing short hairpin RNA targeting RPL34 gene was constructed and used to transfect a human cSCC cell line SCL-1 (shRNA group) , SCL-1 cells transfected with an empty lentivirus vector served as control group, and the knockdown efficiency was verified by real-time quantitative PCR (RT-PCR) and Western blot analysis. At 72 hours after the transfection, flow cytometry was performed to analyze the cell cycle and detect apoptosis of SCL-1 cells, and methyl thiazolyl tetrazolium (MTT) assay to evaluate the cellular proliferative activity of SCL-1 cells. Comparisons between 2 groups were performed by using t test or rank sum test. Results:Immunohistochemical study showed that the cytoplasmic expression score of RPL34 was significantly higher in the cSCC tissues (2.143±1.956) than in the normal control tissues (0.500±0.516, z=3.53, P< 0.05) . RT-PCR showed that the relative mRNA expression of RPL34 in the SCL-1 cells was significantly lower in the shRNA group (0.149±0.016) than in the control group (1±0.018, t=36.95, P< 0.05) ; Western blot analysis revealed that the relative protein expression of RPL34 in the SCL-1 cells was significantly lower in the shRNA group than in the control group. Compared with the control group, the shRNA group showed a significantly increased proportion of S-phase cells ( t=13.76, P< 0.05) , but a significantly decreased proportion of G1-phase cells ( t=36.62, P< 0.05) ; the apoptosis rate was significantly higher in the shRNA group (9.42%±0.16%) than in the control group (4.58%±0.41%, t=19.02, P< 0.05) . MTT assay showed that the cell viability was significantly decreased in the shRNA group (0.815±0.005) than in the control group (1.886±0.005, t=265.91, P< 0.05) after additional 120-hour culture. Conclusion:The RPL34 gene was overexpressed in the cSCC tissues, and knockdown of the RPL34 gene in SCL-1 cells could interfere with cell cycle, decrease their proliferative activity, and promote their apoptosis.
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Objective:To investigate the relationship of polymorphisms in metabolic syndrome-related genes with psoriasis vulgaris (PsV) and their interaction with HLA-C*06:02 in populations of Mongolian nationality.Methods:Totally, 379 PsV inpatients of Mongolian nationality and 518 healthy controls of Mongolian nationality were collected from the Affiliated Hospital of Inner Mongolia Medical University from December 2012 to March 2018. Sixteen previously reported single nucleotide polymorphisms (SNPs) and HLA-C*06:02, which were related to metabolic syndrome and its components, were selected. Next-generation sequencing and polymerase chain reaction-sequence specific primer (PCR-SSP) typing were performed to determine the genotypes of these subjects. Minor allele frequencies of the 16 mutation sites and HLA-C*06:02 were calculated in the PsV group and control group, and chi-square test was used to analyze the differences in the minor allele frequencies of SNPs between the 2 groups.Results:There was no significant difference in the minor allele frequencies of the 16 SNPs susceptible to metabolic syndrome between the Mongolian PsV patients and healthy controls (all P > 0.05), while the minor allele frequency of HLA-C*06:02 significantly differed between the 2 groups ( P = 4.09 × 10 -35, OR = 3.41). Among the HLA-C*06:02-positive subjects, the minor allele frequencies of rs7593730_T and rs6931514_G significantly differed between the 252 PsV patients and 191 healthy controls ( P = 0.016, OR = 0.64; P = 0.041, OR = 1.33, respectively) ; no significant difference was observed in the minor allele frequencies of the 16 SNPs between the PsV patients and healthy controls among the HLA-C*06:02-negative subjects ( P > 0.05) . Conclusion:The SNPs of rs7593730 and rs6931514 may be related to PsV in populations of Mongolian nationality in Inner Mongolia, and may interact with HLA-C*06:02.
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Objective:To analyze culprit drugs and screen susceptible genes in patients of Han nationality with Stevens-Johnson syndrome (SJS) /toxic epidermal necrolysis (TEN) in Inner Mongolia.Methods:A total of 68 patients of Han nationality with confirmed SJS/TEN were collected from Department of Dermatology, the Affiliated Hospital of Inner Mongolia Medical University between 2015 and 2019. DNA was extracted from peripheral blood samples, and PCR was performed to screen HLA-B*5801, HLA-B*1502 and HLA-A*3101 alleles. Clinical data were collected from the patients, and culprit drugs were analyzed according to the genotypes.Results:Among the 68 patients with SJS/TEN, there were 36 males and 32 females, aged 46.06 ± 19.97 (range, 3-84) years. Five cases were positive for HLA-B*5801 allele, of which 4 were induced by allopurinol; 14 cases were positive for HLA-B*1502 allele, of which 5 were induced by carbamazepine, 4 were induced by lamotrigine, and 5 were induced or likely induced by antibiotics and antipyretic analgesics; only 1 case was positive for HLA-A*3101 allele, and the suspected culprit drug was a traditional Chinese medicine injection for promoting blood circulation with unclear ingredients.Conclusions:HLA-B*5801 has a good predictive effect on allopurinol-induced drug eruptions, and HLA-B*1502 on carbamazepine- and lamotrigine-induced drug eruptions. It is recommended to screen susceptible genes before medication. However, the positive rate of HLA-A*3101 was not very high in the population in Inner Mongolia.
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Objective To investigate the association between endoplasmic reticulum aminopeptidase 1 (ERAP1)gene polymorphisms and psoriasis vulgaris (PsV)in a Chinese Han population. Methods Five milliliters of venous blood samples were collected from 289 patients with PsV and 292 human controls of Han nationality after informed consent. Three single nucleotide polymorphisms (SNPs)in the encoding area of the ERAP1 gene, including rs27044, rs30187 and rs26653, were genotyped by ligase detection reaction (LDR). With the PLINK 1.07 package, statistical analysis was carried out by using the chi-square test for comparisons of allele and genotype frequencies between the patient group and control group. The allelic odds ratio (OR)and its 95% confidence interval (CI)were calculated. In addition, haplotype analysis was conducted with the Haploview software. Results The frequencies of rs30187-C and rs26653-G alleles were significantly lower in the patient group (0.460 2 and 0.430 8 respectively), especially in patients with early-onset PsV(0.448 5 and 0.422 7 respectively), than in the control group(0.534 2 and 0.501 7 respectively, all P <0.05). The SNPs rs27044, rs30187 and rs26653 showed strong linkage disequilibrium with each other (r2 ≥ 0.717, D′ ≥0.962). Genotype analysis showed that the frequency of the rs30187 CC genotype was significantly lower in the patient group, especially in patients with early-onset PsV, than in the control group (P < 0.05 and 0.016 7 respectively)under a recessive mode of inheritance. Haplotype analysis revealed that the frequency of the haplotype H4: CTC was significantly increased in the patient group(0.050), especially in patients with early-onset PsV(0.052), compared with the control group (0.022, P < 0.05 and 0.016 7 respectively). Conclusions ERAP1 gene polymorphisms are associated with PsV, especially with early-onset PsV in Chinese Han population. The risk haplotype H4: CTC may be a susceptible factor for PsV.
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Objective To investigate association between polymorphisms of the tumor necrosis factor α-induced protein 3 (TNFAIP3)interacting protein 1 (TNIP1)gene and systemic lupus erythematosus (SLE)in a Chinese Han population. Methods Blood samples were collected from 284 patients with SLE of Han nationality(SLE group)and 630 healthy controls of Han nationality (control group). Ligase detection reaction (LDR)was performed to determine the genotypes of 120 single nucleotide polymorphisms (SNPs)in the TNIP1 gene. Data were analyzed with the PLINK 1.07 package and Haploview software. Results After quality control, data on 105 SNPs underwent statistical analysis finally. Four SNPs including rs3805433, rs12516176, rs6869605 and rs4958882 in the TNIP1 gene were significantly associated with SLE (OR: 1.50 - 1.53, all P < 4.72 × 104), and there was a significant increase in the frequency of rs3805433 C, rs12516176 C, rs6869605 C and rs4958882 G alleles in the SLE group (0.301 - 0.306)compared with the control group (0.221 - 0.225). There was strong linkage disequilibrium between these 4 SNPs (r2 ≥ 0.871, D′ ≥ 0.938). In addition, moderate linkage disequilibrium was observed between these 4 SNPs and a previously reported SLE-related SNP rs10036748 (r2 ≥ 0.073, D′ ≥ 0.868). The frequency of the haplotype H2: CCCGT was significantly higher in the SLE group than in the control group(0.290 vs. 0.210, OR = 1.54, P < 4.72 × 10-4). Conclusion TNIP1 gene polymorphisms are associated with SLE in Chinese Han population.
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Objective To investigate skin manifestations and comorbidities of chronic arsenicosis due to conta?minated drinking water, and to explore their possible risk factors. Methods Data about demographic characteristics, skin manifestations and comorbidities were collected from 95 patients with chronic arsenicosis due to contaminated drinking water in Inner Mongolia, and retrospectively analyzed. A logistic regression model was established to analyze associations of skin manifestations and comorbidities with patients′ gender, age, age at onset of drinking of arsenic?contaminated water, arsenic concentrations in water and duration of arsenic exposure. Results Among the 95 patients, 77 had hyperpigmentation, 75 hypopigmentation, 93 palmoplantar keratoderma, 27 skin cancer, and 8 multiple skin cancer. Five patients were complicated by tuberculosis, 15 by hypertension, 2 by rheumatoid arthritis, 4 by cerebral infarction, 7 by coronary heart diseases, 3 by internal malignancy, 6 by hepatic cirrhosis and 2 by anemia. Logistic regression analysis revealed a significant correlation between hyperpigmentation and arsenic concentrations in water(OR=0.32, 95%CI=0.10-0.98;ORadjusted=0.27, 95%CI=0.08-0.90), between occurrence of hepatic cirrhosis and arsenic concentrations in water (OR=24.67, 95%CI=2.69-226.57;ORadjusted=22.51, 95%CI=2.38-213.11), and between occurrence of coronary heart diseases and duration of arsenic exposure(OR=6.41, 95%CI=1.09-37.88;ORadjusted=8.55, 95%CI=1.21-60.41). Conclusions There is a high incidence of aberrant pigment metabolism, palmoplantar keratoderma and skin cancer in patients with chronic arsenicosis due to contaminated drinking water. Different arsenic concentrations in water and duration of arsenic exposure seem to have different influences on the human body.
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Objective To investigate the association between single nucleotide polymorphisms (SNPs) in the IL2RA-RBM17 region and vitiligo in the Chinese Mongolian population.Methods Five milliliters of venous blood samples were collected from 425 patients with vitiligo (patient group) and 503 healthy human controls (control group) of Mongolian nationality after informed consent,and genomic DNA was extracted with the AxyPrep DNA extraction kit (AP-MX-BL-GDNA-25).Nine SNPs were selected across the IL2RA-RBM17 region,including rs706779,rs3134883,rs7090530,rs12251307,rs4750005,rs3920615,rs4747887,rs4750012 and rs7099083.Ligase detection reaction (LDR) was performed for SNP genotyping.With the PLINK 1.07 and SPSS 11.0 packages,statistical analysis was carried out by the chi-square test for comparisons of allele and genotype frequencies between the patient group and control group.Linkage disequilibrium analysis was performed for 5 SNPs by calculating the r2 and D' values.Haplotype analysis of 5 related SNPs was conducted to investigate differences in haplotype frequencies between the patient group and control group.Results There were significant differences in allele frequencies of 5 SNPs,including rs4750005,rs3920615,rs4747887,rs4750012 and rs7099083,between the patient group and control group (all P ＜ 0.05).Under a dominant mode of inheritance,a significant decrease was observed in the frequencies of GG/GC genotypes of rs3920615,CT/CC genotypes of rs4747887,CT/CC genotypes of rs4750005,TC/TT genotypes of rs4750012 and AG/AA genotypes of rs7099083 in the patient group compared with the control group (all P ＜ 0.005 6).Moderate to strong linkage disequilibrium was observed between the 5 SNPs (D' =0.424-1,r2=0.137-0.985).Haplotype analysis showed that the frequency of a haplotype (H2:CGCTA) was significantly lower in the patient group than in the control group,and the difference reached statistical significance after Bonferroni adjustment (P=0.001 6,OR =0.674).Conclusion SNPs in the IL2RA-RBM17 region are associated with vitiligo in the Chinese Mongolian population.
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Objective To investigate the association between polymorphisms in the tumor necrosis factor α-induced protein 3 (TNFAIP3)-interacting protein 1 (TNIP1) gene and psoriasis vulgaris in a Han population from north China.Methods Totally,465 patients with psoriasis vulgaris (PsV) and 476 healthy human controls were enrolled into the study.Five milliliters of venous blood samples were collected from these subjects after informed consent.Three single nucleotide polymorphisms (SNPs) in the TNIP1 gene,including rs17728338,rs3762999 and rs999556,were selected for genotyping with ligase detection reaction (LDR).With the PLINK 1.07 package,statistical analysis was carried out by using the chi-square test for comparisons of allele frequencies and genotype frequencies between the patient group and control group.The allelic odds ratio (OR) and its 95％ confidence interval (CI) were calculated.In addition,linkage disequilibrium analysis was performed for the three SNPs by calculating the r2 and D' values.Results There was a difference in the allele frequencies of the three SNPs between the patients with psoriasis vulgaris and controls,but the difference was statistically significant in only the allele frequencies of rs17728338,but not in those of the other two SNPs after Bonferroni correction.Under the dominant inheritance model,the genotype frequencies of the 3 SNPs all significantly differed between the patients and controls after Bonferroni correction (all P ＜ 0.016 7).Stratification analysis showed that there was a significant difference in the allele and genotype frequencies of the three SNPs between the patients with a family history and healthy controls (all P ＜ 0.016 7),and the frequency of A allele of rs17728338 was significantly lower in the controls than in the patients with psoriasis vulgaris,patients with early-onset psoriasis vulgaris (n =355),patients with late-onset psoriasis vulgaris (n =107),patients with a family history (n =68),and patients without a family history (n =394) (all P ＜ 0.0167).Strong linkage disequilibrium existed between rs3762999 and rs999556 (r2 =0.910,D' =0.982),and moderate linkage disequilibrium existed between rs17728338 and rs3762999 (r2 =0.371,D' =0.989) as well as rs999556 (r2 =0.353,D' =1).Conclusion The SNPs rs17728338,rs3762999 and rs999556 in the TNIP1 gene were associated with psoriasis vulgaris in the Chinese Han population.
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ObjectiveTo investigate the association of HLA-Cw and -DRB1 alleles with psoriasis vulgaris,and to provide a clue to the study into the etiology of psoriasis.MethodsVenous blood samples were obtained from 81 patients with psoriasis vulgaris collected during 2006-2011 at the Department of Dermatology,First Affiliated Hospital of Inner Mongolia Medical College,as well as 100 age- and gender-matched healthy controls.Both the patients and controls are unrelated Mongolia in Inner Mongolia.PCR with sequence-specific primers(PCR-SSP) technique was used to genotype the HLA-Cw and DRB1 loci.ResultsThe patients with psoriasis vulgaris showed a significantly higher frequency of HLA-Cw*06(0.438 vs.0.175,Pc ＜ 0.01) and DRB1*07(0.241 vs.0.110,Pc ＜ 0.012),but a lower frequency of HLA-Cw*04(0.031 vs.0.150,Pc ＜ 0.01 ) and DRB1*04 (0.093 vs.0.235,Pc ＜ 0.01 ) than the healthy controls did.Increased frequencies of HLA-Cw*06 and DRB1*07 alleles were observed in patients with an onset before 40 years of age and those without a family history,together with a decreased frequency of HLA-Cw*04 and DRB1*04 alleles,compared with the healthy controls(Pc ＜ 0.05).The frequency of HLA-Cw*06 allele was significantly higher in patients with a positive family history and patients with an onset of no younger than 40 years of age than in the healthy controls (both Pc ＜ 0.05).ConclusionsHLA-Cw*06 and -DRB1*07 alleles may be susceptibility determinants to psoriasis vulgaris,while HLA-Cw*04 and -DRB1*04 alleles may be protective factors against psoriasis vulgaris,in Mongolia from Inner Mongolia.HLA-DRB1*07 allele may be a susceptibility gene for psoriasis,while HLA-Cw*04 and -DRB1*04 alleles may be protective factors against psoriasis,in patients with an onset before 40 years of age.