Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in ankylosing spondylitis

OBJECTIVES: To investigate the associations of cytochrome p450 1A1 (CYP1A1) and manganese superoxide dismutase (MnSOD) genes polymorphisms with the susceptibility to AS in Taiwan. METHODS: The polymorphisms of CYP1A1 and MnSOD genes were determined in 70 patients with ankylosing spondylitis (AS) and 93 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) methods. RESULTS: The genotype frequency of CYP1A1 4887C/A was significantly lower in patients with AS than in controls. The phenotype frequency of CYP1A1 4887A also tended to be decreased in patients with AS. There were no significant differences in the genotype, allele, and phenotype frequencies of MnSOD gene polymorphisms between patients with AS and controls. CONCLUSION: CYP1A1 4887A may be a protective factor for the development of AS in Taiwan. However, MnSOD gene polymorphisms are not associated with the susceptibility to AS.     

Cytochrome P450 1A1 and manganese superoxide dismutase genes polymorphisms in reactive arthritis

To investigate the role of cytochrome P450 1A1 (CYP1A1) and manganese superoxide dismutase (Mn SOD) genes polymorphisms in the susceptibility to reactive arthritis, the polymorphisms of CYP1A1 and Mn SOD genes were determined in 43 patients with reactive arthritis following Chlamydia trachomatis infection and 92 healthy controls by polymerase chain reaction (PCR)/restriction fragment length polymorphisms (RFLP) method.

The frequencies of CYP1A1 4887C/A and C/A+A/A were significantly higher in patients with reactive arthritis than in controls. Moreover, the increased frequency of CYP1A1 4887A in patients with reactive arthritis is independent of HLA-B27. The frequency of Mn SOD 1183T/T tended to be increased in patients with reactive arthritis. We also found that the frequency of CYP1A1 4887A was significantly increased in Mn SOD 1183T/T(+) reactive arthritis patients compared with 1183T/T(+) controls.

CYP1A1 4887A may be a risk factor for the development of reactive arthritis, especially in the presence of Mn SOD 1183T/T.     

Manganese superoxide dismutase gene polymorphisms in psoriatic arthritis

The purpose of the present study is to investigate the role of manganese superoxide dismutase (MnSOD) gene polymorphisms in the susceptibility to psoriatic arthritis. MnSOD gene polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphisms method in fifty-two patients with psoriatic arthritis and 90 healthy controls.The genotype frequency of MnSOD 1183C/T was significantly higher in patients with psoriatic arthritis than in controls. In contrast, the frequency of MnSOD 1183T/T was significantly decreased in patients with psoriatic arthritis. The phenotype frequency of MnSOD 1183C was significantly increased in patients with psoriatics arthritis in comparison to healthy controls.Therefore, MnSOD 1183C polymorphisms may be a precipitating factor for the development of psoriatic arthritis.     

Manganese Superoxide Dismutase Gene Polymorphisms in Psoriatic Arthritis

The purpose of the present study is to investigate the role of manganese superoxide dismutase (MnSOD) gene polymorphisms in the susceptibility to psoriatic arthritis. MnSOD gene polymorphisms were determined by polymerase chain reaction/restriction fragment length polymorphisms method in fifty-two patients with psoriatic arthritis and 90 healthy controls. The genotype frequency of MnSOD 1183C/T was significantly higher in patients with psoriatic arthritis than in controls. In contrast, the frequency of MnSOD 1183T/T was significantly decreased in patients with psoriatic arthritis. The phenotype frequency of MnSOD 1183C was significantly increased in patients with psoriatics arthritis in comparison to healthy controls. Therefore, MnSOD 1183C polymorphisms may be a precipitating factor for the development of psoriatic arthritis.     

Natural resistance-associated macrophage protein 1 gene polymorphisms in rheumatoid arthritis

OBJECTIVES: To investigate the association of natural resistance-associated macrophage protein 1 gene (NRAMP1) polymorphisms with rheumatoid arthritis (RA) in Taiwan. METHODS: NRAMP1 polymorphisms were determined from 113 RA patients and 74 healthy controls using the polymerase chain reaction/restriction fragment length polymorphism method. RESULTS: The genotype frequencies of NRAMP1 823 C/C, 1703G/G (543D/D), and 1729+55 del 4 TGTG+/+ (244/244) were significantly higher in patients with RA than in controls. Similar findings were also evident in allele frequencies and allele carriage frequencies of 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244). The associations of these polymorphisms with RA were independent of HLA-DR4. Linkage disequilibria could be found between 823C and 1703G, and between 1703G and 1729+55 del 4 TGTG+. The estimated haplotype frequency of NRAMP1 823C/1703G/1729+55 del 4 TGTG+ was significantly increased in RA patients compared with controls. We also found that patients with 823 C/C had a significantly lower prevalence of rheumatoid nodule than those without 823 C/C. CONCLUSION: NRAMP1 823C, 1703G (543D), and 1729+55 del 4 TGTG+ (244) are precipitating factors for the development of RA in Taiwan. The estimated NRAMP1 823C/1703G/1729+del 4 TGTG+ haplotype is associated with susceptibility to RA. NRAMP1 823 C/C prevents the development of rheumatoid nodule in RA patients.     

Polymorphisms of Genes for Programmed Cell Death 1 Ligands in Patients with Rheumatoid Arthritis

To investigate the role of ligands for programmed cell death 1 (PD-L) in the pathogenesis of rheumatoid arthritis (RA), 129 patients with RA and 125 unrelated healthy controls were enrolled in this study. The PD-L1 and PD-L2 polymorphisms were determined by the method of polymerase chain reaction (PCR)/direct sequencing or PCR/reaction fragment length polymorphisms. The genotype distributions of PD-L1 6777 C/G were not significantly different between the patients with RA and healthy controls. There was also no significant difference in the allele frequencies of PD-L1 6777 C/G polymorphisms between the patients with RA and controls. Similar findings could also be found in the phenotypes and alleles frequencies of PD-L2 47103 C/T and 47139 T/C polymorphisms between the patients with RA and controls. The patients with PD-L1 6777 G had higher prevalence of rheumatoid nodule in comparison with those without PD-L1 6777 G (p = 0.005, OR = 4.0, 95% CI = 1.5–10.9). In contrast, the PD-L2 47103 C/T and 47139 T/C polymorphisms were not related to the occurrence of rheumatoid nodule. This study demonstrated that the PD-L1 and PD-L2 polymorphisms were not associated with susceptibility to RA in Taiwan. PD-L1 6777 G was associated with the prevalence of rheumatoid nodule. Shu-Chen Wang and Chia-Hui Lin contributed equally to this work.     

Inhibitors of kB-like gene polymorphisms in rheumatoid arthritis

OBJECTIVES: To investigate the role of inhibitor of kB-like (IkBL) gene polymorphisms in the pathogenesis of rheumatoid arthritis (RA) in Taiwan. METHODS: One hundred and twenty-nine patients with RA and 110 healthy controls were enrolled in this study. Polymerase chain reaction (PCR)/direct sequencing was used to determine the polymorphisms of IkBL -421 8T/9T, -324 C/G, -262 A/G, and -62 A/T. PCR/restriction fragment length polymorphism was used to determine the IkBL +738 T/C polymorphisms. RESULTS: The genotype distribution of IkBL -421 was significantly different between DR4(+) RA patients and DR4(+) controls (p = 0.02). The allele frequency of IkBL -421 8T was significantly higher in DR4(+) RA patients than in DR4(+) controls (p = 0.004, OR = 7.2, 95% CI = 1.7-29.2). The allele carriage frequency of IkBL -421 8T also tended to be increased in DR4(+) RA patients in comparison with DR4(+) controls (p = 0.07, OR = 14.6, 95% CI = 1.4-147.0). We also found that the allele frequency of IkBL -62 T was significantly higher in RA patients than in controls (p = 0.04, OR = 1.5, 95% CI = 1.1-2.1). The allele carriage frequency of IkBL -62 T tended to be increased in RA patients (p = 0.08, OR = 1.7, 95% CI = 1.0-3.0). The estimated haplotype frequency of IkBL -421 8T/-62 T tended to be increased in RA patients compared with controls (p = 0.07, OR = 1.4, 95% CI = 1.0-2.0). CONCLUSION: The IkBL -62 T may be associated with the development of RA in Taiwan. The IkBL -421 8T may also be related to susceptibility to RA in HLA-DR4(+) individuals. This study shows that the estimated haplotype IkBL -421 8T/-62 T tends to be associated with susceptibility to RA in Taiwan.     

HLA-alloantigen associations in Greek patients with Sj?gren's syndrome

The frequency of HLA-A, -B, and -DR alloantigens was studied in 46 patients with primary Sj?gren's syndrome (pSS), 14 patients with secondary Sj?gren's syndrome (sSS) and rheumatoid arthritis (RA), 26 classical RA patients without clinical or histologic evidence of Sj?gren's syndrome (SS) and 172 normal controls. A statistically significant increase in the frequency of HLA-DR5 alloantigen was observed in the pSS patients, compared with the controls (P less than 0.007, corrected). No differences were detected between pSS patients with or without extraglandular manifestations, nor were any found between anti-Ro(SSA) positive and negative patients. The frequency of HLA-DR3 alloantigen (30%) was not significantly higher in our pSS population than in controls (25%), nor was that of -DR4 in the RA or the sSS patients. The results of the present study indicate that the 'SS susceptibility gene' in Greek patients is linked with the HLA-DR5 expression gene and they support the hypothesis that the fundamental pSS gene may belong to another locus.     

子宫内膜异位症与细胞色素P450 1A1基因A4889G突变的相关性

目的探讨细胞色素P450 1A1(cytochrome P450 1A1,CYP1A1)基因A4889G突变与子宫内膜异位症(endometriosis,EM)的遗传易感性的关系.方法采用等位基因特异性聚合酶链反应的方法,研究了76例EM患者和80名正常对照CYP1A1基因A4889G位点碱基突变.两组均为广东籍汉族妇女.结果 CYP1A1基因A4889G位点等位基因A、G在EM组和对照组分布的差异有显著性(χ2=7.498,P<0.01),其中等位基因G使患EM的相对危险度提高了1.957倍.CYP1A1基因A4889G位点各基因型分布在两组间差异有显著性(χ2=6.915,P<0.05),GG基因型与AA基因型相比患EM的危险度高3.437倍(χ2=5.430,P<0.05).结论 CYP1A1基因A4889G突变等位基因与EM有一定的关联,突变基因型增加了EM的发病风险.     

Variant form of STAT4 is associated with primary Sjögren's syndrome

Single nucleotide polymorphisms in the STAT4 gene have recently been shown to be associated with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). Primary Sj?gren's syndrome (pSS) is a related autoimmune disease thought to have a pathogenesis similar to these diseases. To test the hypothesis that the variant haplotype of STAT4 seen in RA and SLE is also associated with pSS, we genotyped rs7574865, the most strongly disease-associated SNP in the variant STAT4 haplotype, in 124 Caucasian pSS subjects and compared them to 1143 Caucasian controls. The disease-associated T allele was more common in chromosomes of the pSS patients (29.6%) than in controls (22.3%), leading to a P-value for association of 0.01. These results implicate polymorphisms in the STAT4 gene in the pathogenesis of pSS.     

广州地区汉族人群细胞色素P450 1A1和细胞色素P450 2E1基因多态性

目的 探讨广州地区汉族人群细胞色素Ｐ４５０ １Ａ１（ＣＹＰ１Ａ１）和细胞色素Ｐ４５０ ２Ｅ１（ＣＹＰ２Ｅ１）基因的多态性分布规律。方法 用ＰＣＲ－ＲＦＬＰ和等位基因特异性扩增技术,对１５０名广州地区汉族正常人的ＣＹＰ１Ａ１和ＣＹＰ２Ｅ１基因多态性进行了检测,并与其他人群进行了比较。结果 ＣＹＰ１Ａ１基因３’端非翻译区的Ｍｓｐ１多态位点ｍ１（ＭＳＰⅠ－）、ｍ２（ＭｓｐⅠ＋）等位基因频率分别为６２．３     

IkappaBalpha promoter polymorphisms in patients with rheumatoid arthritis

To investigate the role of inhibitor of kappaBalpha promoter polymorphisms in the pathogenesis of rheumatoid arthritis (RA), 140 patients with RA and 115 healthy controls were enrolled in this study. The IkappaBalpha promoter polymorphisms were determined using the polymerase chain reaction/restriction fragment length polymorphisms method. In comparison with IkappaBalpha-826 C/C, the genotype frequency of IkappaBalpha-826 C/T was significantly higher in the patients with RA than that of the controls (P = 0.009, OR = 2.0, 95% CI = 1.2-3.4). The allele frequency of IkappaBalpha-826 T was also significantly increased in patients with RA when compared with that of the controls (P = 0.027, OR = 1.6, 95% CI = 1.1-2.4). In comparison with IkappaBalpha-550 A/A, the genotype frequency of IkappaBalpha-550 A/T was significantly decreased in patients with RA when compared with that of the controls (P = 0.02, OR = 0.2, 95% CI = 0.06-0.8). The allele frequency of IkappaBalpha-550 A was significantly increased in patients with RA (P = 0.007, OR = 5.1, 95% = 1.4-18.2). This study also revealed that the IkappaBalpha-826 T -550 A -519 C haplotype was significantly increased in patients with RA in comparison to that of controls (P = 0.01, OR = 1.8, 95% CI = 1.1-2.8). The IkappaBalpha-826 T and -550 A alleles are associated with susceptibility to RA. Moreover, the IkappaBalpha-826 T -550 A -519 C haplotype is associated with susceptibility to RA in Taiwan.     

Detection of anti-early endosome antigen 1 antibody in sera showing cytoplasmic vesicular staining,taken from patients with connective tissue diseases

An early endosome antigen previously reported by F.T. Mu could be stained on cytoplasmic vesicles of HEp-2 cells. Here, we have investigated autoantibodies against cytoplasmic vesicular antigens, especially against early endosome antigen 1. Twelve sera were selected on the basis of cytoplasmic vesicular staining patterns of HEp-2 cells. Protein-immunoprecipitation using 35S-methionine labeled HeLa lysates, and RNA immunoprecipitation using 32P-labeled HeLa lysates were conducted to characterize the cognate antigens. Nine of 12 sera reacted with proteins in the range of 162-180 kDa, three of which were found to react specifically with the 162 kDa 35S methionine labeled recombinant early endosome antigen 1. These proteins were not associated with common RNA. Although complete clinical information was not available, some of the patients had rheumatoid arthritis(RA). In addition, the RNA-IPP results suggest that other patients included one each with SLE, SSc, polymyositis, and Sj?gren's syndrome. Anti-early endosome antigen 1 antibody was found in 25%(3 of 12) of sera known to stain cytoplasmic vesicles. The reactive sera came mostly from patients with RA. The sera was from one case each of clinical-confirmed RA, SLE and Sj?gren's syndrome.     

Haplotypes in the 5′‐untranslated region of the CYP1A2gene are inversely associated with lung cancer risk but do not correlate with caffeine metabolism

In this study, we analyzed the influence of CYP1A2 genetic variation and enzyme activity on lung cancer risk in a high‐incidence area. A total of 95 lung cancer patients and 196 controls were genotyped for the ?3860G/A, ?3113A/G, ?2467T/delT, ?739T/G, and ?163C/A polymorphisms in the 5′‐untranslated region of the gene. In addition, a subset of 70 patients and 115 controls were phenotyped by high‐performance liquid chromatography determination of the caffeine metabolic ratio (CMR). The ?2467T/delT polymorphism and the CYP1A2*1V haplotype (‐163C>A, ?2467T>delT) were inversely associated with lung cancer risk (odds ratio [OR] = 0.47 [0.2–0.9]; P = 0.02 and OR = 0.13 [0.02‐1.0]; P = 0.04; respectively). In addition, the CYP*1A/*1V and *1F (‐163C>A)/*1D (?163C>A, ?2467T>delT) diplotypes were absent in the patients group, whereas accounting for 7.1% (P = 0.017) and 5.6% (P = 0.037) of controls, respectively. Mean CMR was significantly higher in patients than in controls (10.50 ± 17.31 vs. 6.52 ± 6.26, P = 0.01) but regression analyses did not yield significant ORs for the association with lung cancer risk. Similarly, no significant correlations were found between any genetic variant and enzyme activity. Several CYP1A2 haplotypes and diplotypes containing the ?2467delT variant were associated with lower lung cancer risk; however, they did not correlate with significant changes in CYP1A2 metabolic activity toward caffeine. Environ. Mol. Mutagen., 2013. © 2012 Wiley Periodicals, Inc.     

Solute Carrier Family 11 Member A1 Gene Polymorphisms in Reactive Arthritis

To investigate the role of SLC 11A1 polymorphisms in the development of reactive arthritis, 91 patients with reactive arthritis and 163 healthy controls were enrolled in this study. The SLC 11A1 polymorphisms were determined by the method of polymerase chain reaction/restriction fragment length polymorphism. The genotype distributions of SLC 11A1 274, 823, 1703, and 1729+ 55 del 4 were significantly different between the patients with reactive arthritis and controls. The genotype frequency of SLC 11A1 274C/C was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the SLC 11A1 274C/T showed a significant association with reactive arthritis. The patients with reactive arthritis have a significantly higher frequency of SLC 11A1 823C/C than the controls. However, SLC 11A1 823T/T was resistant to the development of reactive arthritis. The allele frequencies of SLC 11A1 274T and 823C were significantly increased in the patients with reactive arthritis in comparison with those of the controls, independent of HLA-B27. On the contrary, the allele frequencies of SLC 11A1 274C and 823T were significantly decreased in the patients with reactive arthritis. The estimated haplotype frequency of SLC 11A1 274C 823T 1703G 1729+55del 4 TGTG+ was significantly decreased in the patients with reactive arthritis when compared with that of the controls. In contrast, the estimated haplotype frequency of SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ was significantly increased in the patients with reactive arthritis. This study shows that the SLC 11A1 274T and 823C alleles are associated with susceptibility to reactive arthritis independently of HLA-B27 in Taiwan. The SLC 11A1 274T 823C 1703G 1729+55 del 4 TGTG+ haplotype is associated with the development of reactive arthritis in Taiwan. In contrast, the SLC 11A1 274C 823T 1703G 1729+55 del 4 TGTG+ haplotype may be a protective factor.     

Secondary Sjögren''s syndrome and chromosome six markers

Patients with Sj?gren's syndrome (SS) in association with either Rheumatoid Arthritis (RA), Systemic Lupus Erythematosus (SLE) or Sclerodactyly were tested for HLA-A, B and Dr antigens and the phenotypes of the 4th component of complement (CA). Significant associations were identified between HLA-Bw62, Dr4, C4B2.9, C4A8 and females with SS-RA. The MHC antigen frequencies noted for secondary Sj?gren's syndrome differed from those reported for their respective primary diseases and the implications of these observations are discussed.     

CYP1B1基因多态性与子宫内膜异位症易感性的相关研究

目的 研究CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)多态性与子宫内膜异位症(endometriosis,Ems)易感性的关系.方法 采用等位基因特异性聚合酶链反应对55例Ems患者和45例对照组进行CYP1B1基因第2外显子119(G-T)、第3外显子432(C-G)突变分析,探讨Ems的发生与CYP1B1基因多态性之间的相关性.结果 CYP1B1基因密码子119中等位基因G、T在Ems组和对照组分布的差异有统计学意义(P＜0.05),其中等位基因T使Ems发病风险提高2.061倍;CYP1B1基因密码子119G/T各基因型分布两组间差异有统计学意义(P＜0.05),纯合突变(T/T)基因型、杂合突变(G/T)基因型与野生型(G/G)基因型相比,患Ems的危险度分别为2.625倍和3.214倍.以CYP1B1联合野生型GG和CC个体的OR值为1相比,CYP1B基因密码子119杂合型突变(Ala/Ser)合并密码子432野生型个体的OR值为2.976,95%CI:1.129～7.848,P＜0.05.结论 CYP1B1基因第2外显子119(G-T)突变等位基因与Ems的发生有一定关系,突变基因型增加了Ems的发病风险;CYP1B1基因第2外显子杂合型突变(Ala/Ser)联合密码子432野生型能增加Ems的发病风险.     

Identification of candidate genes for Sjögren's syndrome using MRL/lpr mouse model of Sjögren's syndrome and cDNA microarray analysis

Sj?gren's syndrome is a chronic autoimmune disease characterized by focal lymphocytic infiltration of lacrimal and salivary glands, but the precise mechanism of this syndrome is poorly understood. To clarify the mechanism of onset and progression of Sj?gren's syndrome, it is necessary to identify Sj?gren's syndrome-related genes. For this purpose, we used MLR/MpJ-lpr/lpr (MRL/lpr) mouse as a model of human secondary Sj?gren's syndrome and analyzed specific mRNA expression pattern in MRL/lpr mouse salivary glands by in-house cDNA microarray. Among arrayed 2304 genes, 13 genes were isolated as highly expressed genes in MRL/lpr mouse salivary gland in comparison with MRL/MpJ-+/+ (MRL/+) mouse tissue. Subsequently, we performed RT-PCR analysis and confirmed the high expression level of nine genes; caspase3, Ly-6C.2, vimentin, Mel-14 antigen, cathepsin B, mpt1, Laptm5, Gnai2 and UCP2. Five of the nine genes have already been identified in patients with Sj?gren's syndrome or mice models of the syndrome, but the remaining four genes; mpt1, Laptm5, Gnai2, and UCP2 have not been reported previously as Sj?gren's syndrome-related genes. Although, further experiments are necessary to examine the relationship between these four genes and Sj?gren's syndrome, our system of mouse model of Sj?gren's syndrome combined with in-house cDNA microarray is suitable for the isolation of Sj?gren's syndrome-related genes.     

PTPN22, PDCD1 and CYP27B1 polymorphisms and susceptibility to type 1 diabetes in Polish patients

Type 1 diabetes (T1DM) is a common autoimmune disease with a complex genetic background. This study was aimed to investigate the association of PTPN22 G(-1123)C and C1858T, PDCD1 G7146A and CYP27B1 C(-1260)A polymorphisms with T1DM among Polish subjects. The PTPN22 gene encodes lymphoid tyrosine phosphatase, a potent negative regulator of T cell activation. PDCD1 gene gives rise to an inhibitory cell-surface receptor, expressed on activated lymphocytes. CYP27B1 encodes 1-alpha hydroxylase, responsible for conversion of the vitamin D₃ precursor into its active form, involved in the immune function. Polymorphic variants of these genes have previously been associated with various autoimmune disorders. The four polymorphisms were genotyped by PCR-restriction fragment assays in a case–control study comprising 215 T1DM patients and 236 healthy controls. The PTPN22 T1858 allele appeared significantly increased in T1DM compared to the control group (P = 0.004), yielding an OR of 1.73 (95% CI 1.19–2.51). The difference in distribution of C1858T genotypes also demonstrated statistical significance (P = 0.015). The frequencies of PTPN22 G(-1123)C alleles and genotypes did not differ between T1DM cases and controls, although the haplotype comprising both mutant PTPN22 alleles, C(-1123) and T1858, was significantly more frequent in affected individuals (P = 0.003). G(-1123)C and C1858T were in linkage disequilibrium (D′ = 0.98; r² = 0.61 in T1DM and D′ = 0.97; r² = 0.41 in controls). No significant differences in the allele and genotype frequencies of PDCD1 and CYP27B1 polymorphisms were found between patients and controls. This study confirms the association of PTPN22 C1858T polymorphism with T1DM, whereas the effects of PTPN22 G(-1123)C, PDCD1 G7146A and CYP27B1 C(-1260)A seem unlikely, at least in the Polish population.