Association study of zinc finger ZBTB22 single nucleotide polymorphisms and schizophrenia in Han Chinese population / 上海交通大学学报（医学版）

Objective: To explore the association of zinc finger ZBTB22 gene single nucleotide polymorphisms (SNPs) and schizophrenia in Han Chinese population. Methods: A case-control study was designed by genotyping four SNPs (rs3130100, rs1061783, rs1061801 and rs3130099) in 658 schizophrenia patients and 658 healthy controls of Chinese Han origin. SHEsis was used to analyze genotypic and allelic distributions, linkage disequilibrium and haplotype distribution. Results: rs3130100, rs1061783, and rs3130099 showed significant differences between the cases and controls in allele frequencies (P<0. 05 after Bonferroni correction), but no statistically significant differences were found in genotype frequencies after Bonferroni correction. Strong linkage disequilibrium was found among the four SNPs, and the frequency of haplotype TCGA significantly decreased in the schizophrenia patients (P=0.015 after Bonferroni correction). Conclusion: The ZBTB22 SNPs rs3130100, rs1061783 and rs3130099 may be associated with schizophrenia in Han Chinese population.

Association between interleukin-22 genetic polymorphisms and the prognosis of hepatitis B virus related acute-on-chronic liver failure / 中华传染病杂志

Objective To investigate the association between interleukin-22 (IL-22) single nucleotide polymorphisms (SNPs) and the prognosis of hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF).Methods The patients with HBV-ACLF from the First Affiliated Hospital of Fujian Medical University were retrospectively studied.Seven SNP genotypes of IL-22 gene,including rs2227478,rs2227491,rs1179251,rs1179249,rs2227473,rs2227484,and rs11611206,were detected using imLDRTM multiple SNP typing kit and the distribution features of SNP genotypes were described.The relationship between the distribution of SNP genotypes and alleles and the prognosis of ACLF was analyzed.Comparison of genotypes and allele frequencies between groups were performed by chi-square test of R × C table or Fisher's exact tests.Binary logistic regression analysis was used to analyze whether IL-22 gene polymorphisms was an independent prognostic factor for patients with ACLF.Results A total of 122 patients with HBV-ACLF were included in this study.Ninety-two (75.1％) were male and 30 (24.59 ％) were female.Patients were stratified as survival group (90 cases) and non-survival group (32cases) according to the Results of three months follow-up.The genotype distribution of rs2227484 of IL-22 gene was significantly different between the two groups (x2=6.128,P=0.033).The A allele frequency in the non-survival group (15.6％) was significantly higher than that in the survival group (5.6％) with statistically significance (OR=0.318,95％ CI=0.126-0.804,P=0.012).There was no significant difference in the other six SNP genotypes of IL-22 gene between the two groups (all P＞0.05).However,binary logistic regression showed that rs2227484 of IL-22 gene was not an independent risk factor for the short-term mortality in HBV-ACLF patients (adjusted OR=3.102,95％ CI:0.939-10.250,P=0.063).Conclusions The A allele and AA genotype of rs2227484 of IL-22 gene may be associated with a short-term prognosis in patients with HBV-ACLF.

p22phox C242T gene polymorphism and overt diabetic nephropathy: a meta-analysis of 1,452 participants

BACKGROUND/AIMS: The p22phox C242T gene polymorphism (rs4673) may be linked to an increased susceptibility for overt diabetic nephropathy (ODN), but the study results are still inconclusive. METHODS: To explore the relationship between p22phox C242T gene polymorphism and ODN, the current meta-analysis of 707 ODN patients and 745 controls from five individual studies was conducted. The pooled odds ratio (OR) and its corresponding 95% confidence interval (CI) were evaluated by either a random or fixed effect model. RESULTS: In our meta-analysis, a significant relationship between the p22phox C242T gene polymorphism and ODN was found under allelic (OR, 2.760; 95% CI, 1.400 to 5.450; p = 0.004), recessive (OR, 5.080; 95% CI, 1.020 to 25.430; p = 0.05), dominant (OR, 1.700; 95% CI, 1.167 to 2.477; p = 0.006), homozygous (OR, 3.900; 95% CI, 1.022 to 14.889; p = 0.046), heterozygous (OR, 1.523; 95% CI, 1.167 to 1.986; p = 0.002), and additive genetic models (OR, 2.019; 95% CI, 1.232 to 3.309; p = 0.005). CONCLUSIONS: A positive correlation between p22phox C242T gene polymorphism and ODN risk was found. The T allele carriers of p22phox C242T gene polymorphism might be predisposed to ODN.

Association between interleukin-22 genetic polymorphisms and bladder cancer risk

OBJECTIVE:The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated.MATERIALS AND METHODS:A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays.RESULTS:Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer.CONCLUSION:To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding.

Correlation of NADPH oxidase subunit p22phox gene C242T polymorphism with left ventricular hypertrophy in Chinese Korean hypertensive patients / 实用医学杂志

Objective To investigate the relation between the NOSP gene C242T polymorphism and Chinese Korean nationality EH patients with LVH. Methods 108 Chinese Korean controls and 231 Chinese Korean EH patients were enrolled in the research.NOSP gene C242T polymorphism was analyzed by PCR. EH patients were divided into EH and EH+LVH group,all of them were evaluated with CDUS for left ventricular mass index. Results The distribution of NOSP gene C242T polymorphism showed no significant difference compared with controls and EH group.There was significant difference in distribution of CC vs CT+TT genotype between EH and EH+ LVH patients.CC genotype is more dangerous for EH patients combined with LVH than CT and TT genotypes. Conclusions The NOSP gene C242T polymorphism has no relation with EH in Korean nationality people. The NOSP gene C242T polymorphism has relation with EH+LVH; and the CC genotype is a susceptible gene for the Korean EH patients with LVH.

Polymorphisms of SLC22A9 (hOAT7) in Korean Females with Osteoporosis

Among solute carrier proteins, the organic anion transporters (OATs) play an important role for the elimination or reabsorption of endogenous and exogenous negatively charged anionic compounds. Among OATs, SLC22A9 (hOAT7) transports estrone sulfate with high affinity. The net decrease of estrogen, especially in post-menopausal women induces rapid bone loss. The present study was performed to search the SNP within exon regions of SLC22A9 in Korean females with osteoporosis. Fifty healthy controls and 50 osteoporosis patients were screened for the genetic polymorphism in the coding region of SLC22A9 using GC-clamped PCR and denaturing gradient gel electrophoresis (DGGE). Six SNPs were found on the SLC22A9 gene from Korean women with/without osteoporosis. The SNPs were located as follows: two SNPs in the osteoporosis group (A645G and T1277C), three SNPs in the control group (G1449T, C1467T and C1487T) and one SNP in both the osteoporosis and control groups (G767A). The G767A, T1277C and C1487T SNPs result in an amino acid substitution, from synonymous vs nonsynonymous substitution arginine to glutamine (R256Q), phenylalanine to serine (F426S) and proline to leucine (P496L), respectively. The Km values and Vmax of the wild type, R256Q, P496L and F426S were 8.84, 8.87, 9.83 and 12.74 microM, and 1.97, 1.96, 2.06 and 1.55 pmol/oocyte/h, respectively. The present study demonstrates that the SLC22A9 variant F426S is causing inter-individual variation that is leading to the differences in transport of the steroid sulfate conjugate (estrone sulfate) and, therefore this could be used as a marker for certain disease including osteoporosis.

Correlation between polymorphism of PTPN22 gene and pulmonary tuberculosis:a case-control study / 中华微生物学和免疫学杂志

Objective To analyze the correlation between the polymorphism of PTPN22 gene (R620W and R263Q sites)and pulmonary tuberculosis(TB)in Chinese Han population and to investigate the environmental factors associated with pulmonary TB. Methods A case-control study was conducted on 235 patients with pulmonary TB and 251 healthy subjects. The single nucleotide polymorphisms(SNP)of PTPN22 gene at R620W and R263Q sites were detected by the assay of polymerase chain reaction and re-striction fragment length polymorphism(PCR-RFLP). A questionnaire was designed to gather information about tuberculosis-associated environmental factors. Univariate and multivariate logistic analysis were con-ducted. Results Genotype frequencies of PTPN22 R620W(C1858T)SNP were 233(99. 15% ,CC),2 (0. 85% ,CT),0(0% ,TT)in patients with pulmonary TB and 240(95. 62% ,CC),11(4. 38% ,CT), 0(0% ,TT)in healthy subjects. There was a difference with the distribution of PTPN22 C1858T allele be-tween patients with pulmonary TB and healthy subjects[0. 43% vs 2. 19% ,P = 0. 01,odds ratio(OR)=0. 19,95% confidence interval(CI)= 0. 07-0. 35]. Genotype frequencies of PTPN22 R263Q(G788A) were 218(92. 77% ,GG),17(7. 31% ,GA),0(0% ,AA)in patients with pulmonary TB and 248 (98. 71% ,GG),3(1. 29% ,GA),0(0% ,AA)in healthy subjects. The frequencies of G788A allele in patients with pulmonary TB were higher than those in healthy subjects(3. 62% vs 0. 60% ,P﹤0. 01,OR=6. 03,95% CI=2. 12-18. 38). Conclusion The results of this study suggested that the R263Q GG geno-type of PTPN22 gene was associated with the susceptibility to TB in Chinese Han population.

Lack of Association between PTPN22 Gene +1858 C>T Polymorphism and Susceptibility to Generalized Vitiligo in a Turkish Population

BACKGROUND: Vitiligo is an autoimmune polygenic disorder characterized by loss of pigmentation due to melanocyte destruction. The PTPN22 gene +1858 C>T single nucleotide polymorphism (rs2476601) has been shown to be associated with various autoimmune disorders. OBJECTIVE: The aim of this study was to investigate whether the PTPN22 gene +1858 C>T single nucleotide polymorphism is associated with susceptibility to generalized vitiligo in a Turkish population. METHODS: One hundred and seven patients with generalized vitiligo, and one hundred and twelve gender-, age-, and ethnic-matched controls were enrolled in the study. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: The PTPN22 +1858 C>T genotype and allele frequencies of the generalized vitiligo patients did not differ significantly from those of healthy controls. CONCLUSION: We found no association between the PTPN22 +1858 C>T gene polymorphism and vitiligo susceptibility in Turkish generalized-vitiligo patients.

Protein tyrosine phosphatase non-receptor type 22 gene polymorphism C1858T is not associated with leprosy in Azerbaijan, Northwest Iran.

BACKGROUND: Leprosy (Hansen’s disease) is a human chronic granulomatous infectious disease caused by Mycobacterium leprae. Several types of study support a role for host genetics in susceptibility to leprosy. The protein tyrosine phosphatase non‑receptor type 22 (PTPN22) gene encodes an intracellular lymphoid protein tyrosine phosphatase that has been shown to play a negative regulatory role in T‑cell activation. AIMS: The aim of the present study was to find out associating the PTPN22 C1858T (R620W) polymorphism and leprosy in the Azeri population from Northwest Iran. MATERIALS AND METHODS: A total of 153 treated leprosy patients and 197 healthy and ethnic matched controls entered this study. We used restriction fragment length polymorphism method to type PTPN22 C1858T polymorphism. RESULTS: There was no significant difference in distribution of genotype and allele frequencies of PTPN22 C1858T polymorphism between leprosy patients and controls (P = 0.641 and 0.645; respectively). Moreover, there was no significant association between different clinical findings (karnofsky performance status score, clinical forms and manifestations of leprosy) and PTPN22 C1858T polymorphism. Data showed a low frequency of the minor (T) allele by 2.3% in leprosy and 1.5% in healthy individuals. CONCLUSIONS: The PTPN22 C1858T (R620W) is not relevant in susceptibility to leprosy in the Azeri population of Northwest Iran.

Association between haplotype of interleukin-22 gene promoter and susceptibility to pulmonary tuberculosis / 中华临床感染病杂志

Objective To investigte the association between haplotype of the promoter of interleukin-22 (IL-22) gene and the susceptibility to pulmonary tuberculosis.Methods Clinical data of 479 patients with pulmonary tuberculosis was collected from Shenzhen Third People's Hospital during January 2009 and December 2010,and 358 healthy controls were also enrolled in the study.Single nucleotide polymorphisms (SNPs) of IL-22 (rs2227472,rs2227473,rs2227478,rs2227483,rs2227485,rs2227486,rs2227487 and rs2227513) were genotyped using the Sequenom MassARRAY iPLEX Platform.The allele frequency and odds ratio (OR) of genotypes of SNPs and haplotypes of IL-22 were calculated; the association between the haplotypes of IL-22 and the susceptibility to pulmonary tuberculosis was analysis.Results rs2227472,rs2227473,rs2227478,rs2227483 and rs2227485 were associated with the susceptibility to tuberculosis (OR =0.796,0.653,0.769,0.762 and 0.816 ; x2 =4.594,6.921,5.256,5.089 and 3.827 ; P ＜0.05 or P ＜ 0.01).The frequencies of haplotypes (CTFAA and TATGG) in case group were significantly different from those in control group (CTFAA:0.004 vs.O.032,OR =0.04,x2 =384.623,P＜0.01; TATGG:0.522 vs.0.460,OR=1.49,x2 =6.690,P=0.01).Conclusions Five SNPs of IL-22 (rs2227472,rs2227473,rs2227478,rs2227483,rs2227485) and 2 haplotypes (CTTAA and TATGG) are associated with the susceptibility to pulmonary tuberculosis.Haplotype CTTAA is a protective factor for susceptibility to pulmonary tuberculosis,whereas haplotype TATGG is a risk factor.

The determination of a new single nucleotid polymorphism intron 5 (+4668) with high-resolution melting technology in gout patients / 中华风湿病学杂志

Objective To investigate a new single nucleotid polymorphism (SNP) intron5(+4668C/T) in SLC22A12 in primary gout patients and the association between clinical characteristics and genotypes. Methods One hundred and one primary gout patients and 186 healthy subjects were recruited into this study. Blood pressure, body mass index (BMI) was recorded. Serum uric acid, glucose, lipid and creatinine were detected. DNA was extracted from peripheral blood to amplify the fragment located in intron 5. The genotypes of SLC22A12 can be detected with high-resolution melting (HRM) assay, followed by sequencing analysis. Chi-square test was used for statistical analysis. Results ① A new SNP in intron 5 of SLC22A12 was identi-fied successfully by HRM, which was defined as intron 5 (+4668C/T). CC, CT and TT genotypes were unam-biguously distinguished with HRM technology, which was fully concordant with sequencing. ②The genotypes of CC, CT and TT in male and female groups were 28.1%, 33.7%, 38.2% and 20.0%, 47.1%, 32.9%, respectively.③ However, no significant differences of genotype distribution were found concerning BMI, blood pressure, creatinine, total cholesterol and triglyceride in both male group and female group. But the serum uric acid levels in the CC genotype were significantly higher than those with the CT+TT genotypes. ④ The genotype frequencies of CC and CT+TT in high uric acid group were remarkably different from those in low uric acid group (21.2%, 78.8%,; 35.0%, 65.0%; P<0.05). Conclusion A new SNP has been successfully discovered with HRM technology with simplicity, rapidity and accuracy. T allele of intron 5 (+4668C/T) may be a genetic protective factor for hyperuricemia among Chinese population.

Association between single nucleotide polymorphisms of SLC22A4 and RUNX1 gene with rheumatoid arthritisand ankylosing spondylitis in Chinese Han ethnicity / 第二军医大学学报

Objective: To analyze the correlation between single nucleotide polymorphisms (SNP) of solute carrier family 22 member4 (SLC22A4) and runt-related transcription factor 1 (RUNX1) gene with rheumatoid arthritis (RA) and ankylosing spondylitis(AS) in Chinese Han ethnicity. Methods: Case-control studies were conducted with an RA cohort (104 RA patients and 109 healthy subjects) and an AS cohort (278 AS patients and 417 healthy controls). Three SNPs of SLC22A4 gene and an SNP of RUNX1 gene were genotyped by direct sequencing; we also assessed whether these alleles and genotypes were associated with RA and AS. Results: No significant differences in the distribution of the alleles and genotypes of SLC22A4 and RUNX1 polymorphisms were found between patients with RA and AS and healthy controls. Conclusion: Our results suggest that SLC22A4 and RUNX1 polymorphisms analyzed in the present study are not the susceptible genes for RA and AS in Chinese Han ethnicity.

Study on the relationship between polymorphism of PTPN22 and Graves'disease of Han nationality in Chongqing area / 重庆医科大学学报

Objective:To investigate the relationship between the polymorphism of PTPN22 gene exon14 C1858T and Graves' disease(GD)in Han Group in Chongqing area.Methods:The PTPN22 gene C1858T alleles were typed by polymerase chain reaction based restriction fragment length polymorphism(PCR-RFLP)method in 283 GD patients and 218 normal subjects.The comparisons of genotype and allele frequencies were made between GD patients and normal group.Results:The frequencies of CC、CT and TT genotype in GD patients and normal group were 97.2%,2.8%,0% respectively,Their ?2 were 0.139 and 0.002 respectively,and p were 0.71 and 0.96 respectively.There was no significant difference of the genotypes and allele frequencies at position-1858 of PTPN22 in GD patients compared with those of normal group,and there was no TT genotype and a few T alleles.Conclusion:There is no correlation between the polymorphism of PTPN22 gene exon14 C1858T and GD patients in Han nationality of Chongqing.