CTLA4 +49 A/G and CT60 polymorphisms in Dutch coeliac disease patients

Coeliac disease is an autoimmune disorder, characterised by villous atrophy of the small intestine, which results from a T-cell-mediated response to gluten-derived peptides. The cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) is involved in the regulation of T-cell activation and the CTLA4 +49 A/G polymorphism in exon 1 has been implicated in several autoimmune disorders, including coeliac disease. However, this polymorphism was recently excluded as being the causal variant in Graves' disease, autoimmune hypothyroidism and type I diabetes mellitus. This causal variant was mapped to the 3' region of CTLA4, with the CT60 polymorphism showing the strongest association. The aim of this study was to determine the role of the CTLA4 gene in coeliac disease in the Dutch population. The +49 A/G and CT60 polymorphisms were genotyped in a case-control cohort of 215 patients and controls. The frequency of the +49 G-allele was increased in cases, although not significantly. However, the frequency of the CT60 G-allele was increased with borderline significance in coeliac disease patients (P = 0.048), although the genotype distributions did not show a significant difference between cases and controls. These results indicate the involvement of the CTLA4 gene in coeliac disease development. The haplotype carrying the CT60 G-allele was shown to be associated with lower mRNA levels of the soluble CTLA-4 isoform, providing a possible mechanism for the T-cell-mediated destruction of the small intestine.     

The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.     

CTLA-4 +49 A/G dimorphism in Italian patients with celiac disease

The chromosome region 2q33, which contains the cytotoxic T lymphocyte antigen-4 (CTLA-4) gene, has been reported in linkage and association with celiac disease (CD). In the present work we have tested the association between the polymorphism of the CTLA-4 exon 1 and susceptibility to CD in an Italian population, using case-control and family-based approaches. The +49 A/G dimorphism was analyzed in 86 patients, 144 ethnically matched controls, and 113 nuclear families by the polymerase chain reaction-restriction fragment length polymorphism method. A significantly higher frequency of the CTLA-4 +49A allele was observed in patients when compared with controls (p = 3 x 10(-2)). The segregation analysis in the 113 trios showed a preferential transmission of the A allele to the probands (chi(2)(TDT) = 4.85). When the patients were stratified according to the presence/absence of the high-risk human leukocyte antigen-DQ2 heterodimer, a significant difference was observed between the two groups, that is, the A allele was increased in the subjects without the DQ2 heterodimer (88.9% vs 73.5%, p = 8.3 x 10(-3)). The A allele was transmitted from heterozygous parents to eight of nine DQ2-dimer-negative patients. These data support CTLA-4 as a predisposing gene for CD in an Italian population with a prominent role in patients not carrying the high-risk human leukocyte antigen-DQ2 molecules.     

CTLA-4 +49A/G polymorphism is associated with Behçet's disease in a Tunisian population

The involvement of excessive T-helper cell functions in the pathogenesis of Behçet's disease (BD) has been reported. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays a role in T-cell downregulation. In this report, we investigated the possible association between BD patients and the CTLA-4 +49A/G polymorphism in Tunisian population. A total of 135 Tunisian BD patients and 151 healthy blood donors from the same geographic area were genotyped by polymerase chain reaction for the CTLA-4 +49 A/G polymorphism. A highly significant difference between Tunisian BD patients and healthy controls was found regarding the distribution of CTLA-4 +49 A allele [ P  < 10⁻⁷; χ² = 75.63; odds ratio (OR) = 4.63; 95% confidence interval (CI) = 3.20–6.72] and genotype frequencies ( P  < 10⁻⁷; χ² = 71.02). Furthermore, in the BD group, the A allele was predominant in males (76.3%) when compared with females (62%), ( P  = 0.014; χ² = 5.97; OR = 1.99; 95% CI = 1.10–3.59). No relationship was found between the studied genotype and clinical manifestations. Our results show a gene dose effect of the A allele on the BD. The A allele exerts a stronger effect on disease susceptibility in males compared with females.     

No association of the A260G and A386G DAZL single nucleotide polymorphisms with male infertility in a Caucasian population

BACKGROUND: The human DAZ gene family includes two autosomal genes, BOULE and DAZL, and a Y-chromosomal DAZ gene cluster. All are RNA-binding proteins and assumed to be master regulators of germline gene expression. We have investigated the impact of two DAZL polymorphisms, located at nucleotide positions 260 (SNP 260) and 386 (SNP 386), on the fertility of Caucasian men. These single nucleotide polymorphisms (SNPs) have been described previously to be associated with spermatogenic failure. METHODS: Blood samples were collected and genomic DNA was extracted from 165 normozoospermic men and 202 oligo- or azoospermic patients, of whom 28 displayed an AZFc deletion. The frequencies of A or G allelic variants in SNP 260 and 386 were analysed via TaqMan allelic discrimination assays. In both cases, the A to G transition leads to a threonine to alanine change. RESULTS: A total of 24.2% of the controls showed a heterozygous nucleotide variant (AG) for the SNP 260 and the remaining 75.8% were homozygous for A. In the AZFc-deleted group, this distribution was significantly different, with 39.3% for AG, 57.1% for AA and 3.6% for GG. However, the increased heterozygosity was not correlated with sperm counts and morphology. The patients without deletions displayed a similar allelic pattern to the controls (24.1% AG/75.9% AA). For SNP 386, only the AA nucleotide variant was found in all subjects studied and in no case was the previously described heterozygous AG variant found. CONCLUSION: In a selected Caucasian population, the DAZL SNP 386 is completely absent and SNP 260 is not associated with spermatogenic failure and therefore does not represent a molecular marker for genetic diagnosis of male infertility.     

CTLA-4 +49 A/G gene polymorphism in Croatian and Slovenian multiple sclerosis patients

Polymorphisms in the CTLA-4 gene are known to be important in several autoimmune diseases, including multiple sclerosis (MS). Previous studies on the impact of CTLA-4 +49 A/G gene polymorphism have given contradictory results. We investigated the possible influence of this polymorphism on MS susceptibility and disease behaviour in Croatian and Slovenian populations. Genotyping was performed in 367 patients with MS and 480 control subjects using PCR-RFLP method. The G allele was present in 216 (58.9%) patients with MS vs. 282 (58.7%) healthy controls (P = 0.975, OR = 1.01, 95% CI = 0.76-1.32). No significant differences were observed in CTLA-4 +49 A or G allele distribution between patients and controls, indicating that this polymorphism does not influence susceptibility to MS in the surveyed populations. No correlation was observed between G allele carrier status and age at disease onset, disease course or severity.     

MTHFD 1958G>A and MTR 2756A>G polymorphisms are associated with bipolar disorder and schizophrenia

BACKGROUND: The etiology of bipolar disorder (BD) and schizophrenia is very complex. Polymorphic variants of genes encoding enzymes of the monoaminergic may be involved in development of BD and schizophrenia. Therefore, we examined the prevalence of 1958G>A polymorphism of MTHFD1 gene, encoding trifunctional folate enzyme 5,10-methylenetetrahydrofolate dehydrogenase, 5,10-methenyltetrahydrofolate cyclohydrolase and 10-formyltetrahydrofolate synthetase (MTHFD1), and 2756A>G variant of methionine synthase (MTR) gene in patients with BD (n=200), schizophrenia (n=200) and in controls (n=300). OBJECTIVE: We investigated the genotypic and allelic frequencies of MTHFD1 1958G>A (R653Q) and MTR 2756A>G (D919G) gene polymorphisms in a group of bipolar (n=200) and schizophrenic patients (n=200), as well as in controls (n=300). METHODS: The distributon of genotypes in all groups was tested for deviation from Hardy-Weinberg equilibrium (HWE). The Pearson's chi-square (chi) test and Fisher's exact test were applied to assess differences in the genotypic and allelic (respectively) distribution between groups of patients and controls. MAIN RESULTS: We found that MTHFD1 1958AA or 1958AG genotypes constitute risk factors for development of bipolar disorder type I (BDI) or schizophrenia with odds ratios (OR)=1.743 (95% CI=1.211-2.508; P=0.0027; P (corr)=0.0054) and 2.667 (95% CI=1.845-3.854; P=0.0001; P (corr)=0.0002), respectively. In the same groups, the MTR 2756GG or 2756AG genotypes also constitute significant risk factors in occurrence of BDI and schizophrenia with OR=1.621 (95% CI=1.130-2.326; P=0.0086; P (corr)=0.0172) and 1.556 (95% CI=1.085-2.232; P=0.0160; P (corr)=0.032), respectively. Gender classification of patients indicated significant association only of MTHFD1 1958A allele with BDI and schizophrenia in the male patients OR=1.838 (95% CI=1.114-3.031; P=0.0166; P (corr)=0.0332) and OR=3.964 (95% CI=2.358-6.663; P=0.0001 P (corr)=0.0002), respectively. CONCLUSION: Since MTHFD and MTR genes are located in 14q24 and 1q43 loci, our findings support the significance of chromosomes 14q and 1q in etiopathogenesis of bipolar disorder and schizophrenia.     

CT60 single nucleotide polymorphism of the CTLA-4 gene is associated with susceptibility to Graves' disease in the Taiwanese population

Graves' disease (GD) is an autoimmune disease but the underlying etiology has not been completely elucidated. Genetic susceptibility has been believed to play a major role. Recent studies showed that the CT60 single nucleotide polymorphism (SNP), which is in the 3'-noncoding region of the CTLA-4 gene, is strongly associated with some immune-mediated diseases. The aim of this study was to test for association between GD susceptibility and polymorphisms of CTLA-4 (ie, the CT60 SNP and the exon 1 +49 SNP) in the Taiwanese population. Our results demonstrate significant differences in the frequencies of the genotypes and alleles between 107 GD patients and 101 control subjects in the CT60 and exon 1 +49 SNPs (p <0.05). Significant differences in phenotypes were only found for CT60 SNP (78.4% vs 67.8% between patients and controls; chi2 = 3.93, p = 0.047). Furthermore, we found that the G/G genotype of both CT60 and exon 1 +49 was associated with increased risk for GD (p = 0.022, OR = 1.97). Significant linkage disequilibrium was found between the CT60 SNP and the exon 1 +49 SNP in both GD patients and control subjects (D' = 1.00). Because of tight linkage disequilibrium, a combination of these SNPs enhanced the role of the CTLA-4 gene in GD. The frequency of the disease-susceptible G allele of CT60 was comparable to that in Japanese and higher than in Caucasians. In conclusion, we provide evidence that CT60 SNP is associated with susceptibility to GD in the Taiwanese population.     

Association of a CTLA-4 3' untranslated region (CT60) single nucleotide polymorphism with autoimmune thyroid disease in the Japanese population

The etiology of the autoimmune thyroid diseases (AITDs), Graves' disease (GD) and Hashimoto's thyroiditis is largely unknown. However, genetic susceptibility is believed to play a major role. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene, encoding a negative regulator of the T-lymphocyte immune response, had been reported to be associated and/or linked to AITD. Recently, AITD susceptibility in the Caucasians was mapped to the 6.1-kb 3'UTR of the CTLA-4 gene, in which the single-nucleotide polymorphism (SNP), CT60, was most strongly associated with AITD. In order to determine the association of the CTLA-4 gene with AITD in the Japanese, case-control association analysis for the CT60 of the CTLA-4 gene using 264 AITD patients and 179 healthy controls was done. The frequency of the disease-susceptible G allele of the CT60 of the Japanese control was higher than that of the Caucasians (72.6 vs. 52.3%). However, the G allele of the CT60 was associated with GD (84.0 vs. 72.6%, P=0.0008) and AITD (80.1 vs. 72.6%, P=0.009) in the Japanese. Furthermore, the G allele of the CT60 was associated with the increased risk for GD [P=0.004, odds ratio (OR)=2.0] and AITD (P=0.03,OR=1.6) in a recessive model. These results suggested that the CTLA-4 gene is involved in the susceptibility for GD and AITD in the Japanese.     

Association between IL-18 gene promoter polymorphisms and CTLA-4 gene 49A/G polymorphism in Japanese patients with type 1 diabetes

Interleukin-18 (IL-18) is a potent proinflammatory cytokine which is strongly associated with the development of diabetes in NOD mice. To test the putative involvement of IL-18 gene polymorphism in predisposition to human type 1 diabetes, the SNPs at position -607 (C/A) and -137 (G/C) in the promoter region of IL-18 gene were analyzed by sequence-specific PCR in 116 patients with type 1 diabetes and 114 normal controls. A linkage disequilibrium found only three of the four possible haplotypes defined by these SNPs. The distribution of the IL-18 gene genotypes at position -607 was significantly different between patients with type 1 diabetes and normal controls (P=0.023). Furthermore, there was a significant increase in haplotype 1 (-607C/-137G) in the patients compared with controls (P=0.006). The association study of the susceptible CTLA-4 genotype (GG at nucleotide position 49 in exon 1) or HLA-DR4-DQB1*0401 and type 1 diabetes showed that the predisposing IL-18 gene haplotype modulates the risk on CTLA-4 GG genotype, but not on HLA-DR4-DQB1*0401 haplotype. Among subjects carrying the CTLA-4 GG genotype, the frequency of IL-18 haplotype 1 in patients with type 1 diabetes was significantly higher than that in controls (91% vs. 71%, P=0.012). However, IL-18 haplotype 1 was not frequent in patients who do not exhibit the CTLA-4 high-risk genotype. These results suggest that the IL-18 gene polymorphism is associated with a type 1 diabetes susceptibility, and there might be a gene-gene interaction between IL-18 gene with susceptible CTLA-4 gene.     

Promoter region -318 C/ T and -1661 A/G CTLA-4 single nucleotide polymorphisms and type 1 diabetes in North Indians

Single nucleotide polymorphisms (SNPs) of the CTLA-4 gene have been associated with manifestation of type 1 diabetes in several populations. We assessed the association of five SNPs present in the CTLA-4 gene [-318C/T, -1661A/G and -1722C/T in the promoter region, +49A/G in exon 1 and CT60 in the 3' untranslated region (UTR) region] with type 1 diabetes in North Indian subjects. Genotyping was performed in the patients (n = 130) and the healthy control (n = 180) subjects by polymerase chain reaction-fragment length polymorphism analysis using MseI, BbvI, BstEII and NcoI restriction endonucleases for the -318, -1661, -1722, +49 and CT60 SNPs, respectively. The frequency of G alleles at -1661 locus was significantly higher in the patient group compared with the control subjects. Although the frequency of T alleles at -318 SNP was significantly higher in patients with type 1 diabetes compared with the controls, it did not remain significant after Bonferroni correction for the number of alleles tested. The frequencies of C/T alleles and genotypes at -1722C/T and G allele at +49A/G and CT60 SNPs were not significantly different between the patient and the control groups. Of the various possible haplotypes constructed using the five genetic loci tested (-318, -1661, -1722, +49, CT60), the frequency of 'TGTAG' haplotype was significantly higher in the patients when compared with the controls. The results of the present study indicate that the presence of G allele at -1661 locus at the CTLA-4 gene (IDDM12 locus) is associated with increased susceptibility to type 1 diabetes in North Indians, whereas A allele is protective.     

Polymorphisms at +49A/G and CT60 sites in the 3' UTR of the CTLA-4 gene and APECED-related AIRE gene mutations analysis in sporadic idiopathic hypoparathyroidism

Autoimmune diseases such as Graves' disease and type 1 diabetes have been linked with +49A/G and CT60 single nucleotide polymorphisms (SNPs) in the 3' UTR of the cytotoxic T-lymphocyte antigen-4 (CTLA-4) gene. Both these SNPs are functionally relevant and linked with T-lymphocyte activation. Hypoparathyroidism is seen in 70% of patients with autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome (APECED). Although calcium sensing receptor autoantibodies (CaSRAb) and generalized activation of T lymphocytes are reported among patients with sporadic idiopathic hypoparathyroidism (SIH), CTLA-4 gene SNPs and APECED-related autoimmune regulator (AIRE) gene mutations have not been assessed in them. We studied lead CTLA-4 gene SNPs and APECED-related AIRE gene mutations in 73 patients with SIH and 114 healthy subjects. The CTLA-4 gene SNPs +49A/G in exon 1, CT60A/G in 3' UTR and -318C/T in the promoter region were genotyped by polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) using BstEII, NcoI and MseI endonucleases, respectively. The APECED-related AIRE gene mutations, which is R257X (Finn-major) in exon 6, 4-bp insertion and 13-bp deletion in exon 8, and Iranian Jews population 'Y85C' mutation in exon 2, were studied by PCR-RFLP (Taq-I), PCR and nucleotide sequencing, respectively. CaSRAb were studied by immunoblotting. The frequencies of CTLA-4 A/A(49), A/G(49) and G/G(49) genotypes in the patients (47.9%, 38.4% and 13.7%) and controls (45.6%, 39.5% and 14.9%, respectively) and the frequencies of CT60 A/A, A/G, and G/G genotypes in the patient (42.4%, 37.0% and 20.6%) and the control (38.6%, 40.4% and 21.0%, respectively) groups were not significantly different. The frequencies of various haplotypes including genetic loci +49A/G and CT60 and frequencies of G alleles at these positions were comparable between patient and the control groups and its presence did not correlate with clinical and biochemical indices of the disease. None of the patients had APECED-related AIRE gene mutations. Lack of significant difference in the pattern of CTLA-4 A/G(49) and/or CT60A/G genotypes and absence of common APECED syndrome-related AIRE gene mutations among patients and controls suggest that these sites do not play a role in the development of the SIH.     

Lack of association between an exon 1 CTLA-4 gene polymorphism A(49)G and multiple sclerosis in a Polish population of the Lower Silesia region

Multiple sclerosis (MS) a chronic inflammatory demyelinating disease of the central nervous system is believed to have a T cell-mediated autoimmune etiology. The cytotoxic T lymphocyte antigen 4 (CTLA-4) gene is a strong candidate for the involvement in autoimmune diseases because CTLA-4 plays an important role in the downregulation of the early and late stages of T cell activation and the maintenance of peripheral T cell tolerance. To examine the genetic association of the CTLA-4 gene locus with MS, we analyzed an exon 1 CTLA-4 gene polymorphism A(49)G in 102 unrelated Polish MS patients in the Lower Silesia region and 101 age- and sex-matched healthy subjects. The distribution of CTLA-4 exon 1 A(49)G genotype, phenotype and allele frequencies did not differ between patients with MS and healthy subjects.     

中国人自身免疫性肝病相关性 CTLA-4基因多态性研究

目的　探讨细胞毒性 T细胞相关抗原 - 4 (cytotoxic T lymphocyte- associated antigen- 4 ,CTL A- 4 )基因启动子 - 318和第 1外显子区第 4 9位基因多态性与中国人自身免疫性肝炎 (autoimmunehepatitis,AIH)、原发性胆汁性肝硬化 (primary biliary cirrhosis,PBC)发病的相关性。方法　应用限制性片段长度多态性方法分析 6 2例 AIH和 77例 PBC患者外周血单核细胞基因组 DNA CTL A- 4启动子 -318T/ C、第 1外显子区第 4 9位基因 A/ G多态性 ,并与 16 0名正常对照比较。结果　 AIH组 CTL A- 4启动子 - 318位 T/ C基因型分布与对照组比较差异无显著性 ,但 C等位基因频率明显高于正常对照组 (P=0 .0 2 ,OR=2 .4 3)。 PBC患者 CTL A- 4第 1外显子区第 4 9等位基因分布与正常对照组比较差异非常显著(P=0 .0 0 6 ) ,PBC患者 G等位基因频率明显高于正常组 (P=0 .0 0 4 6 ,OR=1.8)。联合分析 CTL A- 4启动子与第 1外显子的基因多态性分布 ,虽然 AIH组和 PBC组 GG- CC型携带率均比正常人高 (AIH组 :32 .3% ,PBC组 :37.7% ,对照组 :2 2 .5 % ) ,但是统计学分析结果均显示两组患者与正常人差异无显著性。结论　 CTL A- 4启动子 - 318和第 1外显子区第 4 9位基因多态性可能与中国人 AIH、PBC易感性相关。     

Association of -318 C/T and +49 A/G cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms with a clinical subset of Italian patients with systemic sclerosis

Systemic sclerosis (SSc) is a complex and heterogeneous autoimmune disorder with a multi-factorial pathogenesis. Like other autoimmune disorders, the possible role of specific cytotoxic T lymphocyte antigen-4 (CTLA-4) gene polymorphisms in predisposing to SSc has been hypothesized, but it remains controversial. CTLA-4 promoter (-318C/T) and exon 1 (+49 A/G) polymorphisms have been analysed in 43 Italian females with SSc and in 93 unrelated matched healthy controls by a newly designed tetra-primer amplification refractory mutation system-polymerase chain reaction (T-ARMS-PCR) method. No significant association has been found with either polymorphisms.Nevertheless, SSc patients without concomitant Hashimoto's thyroiditis (HT) were carrying both the -318T allele (P = 0.031) and the +49 G allele (P = 0.076) more frequently than SSc patients with HT [defined by positivity for anti-thyroperoxidase (TPO) and anti-thyroglobulin (TGA) autoantibodies] than controls. Haplotype analysis confirms this association (P = 0.028), and suggests the predominant role of the -318T, whereas that of the +49 G, if any, seems weak. Thus, in Italian SSc patients the CTLA-4 -318C/T promoter polymorphism appears to be associated with the susceptibility to develop SSc without thyroid involvement. Larger studies are needed to confirm these findings and to clarify whether the -318C/T polymorphism is the functional responsible or whether it reflects the presence of another linked genetic element in the same chromosomal region.     

Meta-Analysis: The Relationship Between CTLA-4 +49 A/G Polymorphism and Primary Biliary Cirrhosis and Type I Autoimmune Hepatitis

Objectives: CTLA-4 exon-1 +49A?>?G (rs231775) polymorphism has been reported to influence the risk for primary biliary cirrhosis (PBC) as well as type I autoimmune hepatitis (AIH-1) in many studies; however, the results still remain controversial and ambiguous. This study aimed to determine more precise estimations for the relationship between CTLA-4 +49 A?>?G polymorphism and the risk for PBC and AIH-1 by using a meta-analysis.

Design and Methods: PubMed, EMBASE and MEDLINE were searched. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to estimate the strength of the association.

Results: Fifteen studies including 3661 patients with PBC and 4427 controls as well as seven studies including 1270 patients with AIH-1 and 1614 controls were identified. Our pooled analysis revealed that G allele of CTLA-4 gene +49A/G polymorphism may confer an increased risk of PBC in overall (p?=?0.001, OR?=?1.29; 95% CI?=?1.13–1.47) and Caucasians (p?=?0.001, OR?=?1.32; 95% CI?=?1.21–1.44). At genotypic level, the codominant, dominant and recessive models showed no significant association with PBC. With respect to AIH-1, the AG genotype demonstrated a trend for association with increased risk of AIH-1 (p?=?0.04, AG vs. AA, OR?=?1.20; 95% CI?=?1.01–1.43). However, the CTLA-4 alleles as well as genotypes in dominant and recessive models were not associated with a risk for AIH-1 in both Caucasians and Asians.

Conclusions: This meta-analysis concluded that the CTLA-4 G allele and the AG genotype were associated with an increased risk for PBC and AIH-1, respectively, suggesting the CTLA-4 +49 A/G polymorphism as a candidate of susceptibility locus to PBC and AIH-1.     

广西汉族人群中缺氧诱导因子3A基因rs11672731和rs2072491 的多态性

目的 探讨缺氧诱导因子3A(HIF3A)在广西汉族人群中的分布特征,并比较它们与不同人群的分布差异.方法 我们对纳入本研究的286例广西人rs1 1672731和rs2072491位点采用单核苷酸多态性分型检测(SNPscan)技术进行基因分型检测,统计学分析基因型和等位基因频率与人类基因组单体型图(HapMap)公布...     

HSP70-hom gene single nucleotide (+2763 G/A and +2437 C/T) polymorphisms in sarcoidosis

In the present study, two coding polymorphisms within the heat shock protein 70‐hom gene (HSP70‐hom) were analysed. One hundred and thirty‐eight individuals were studied, including 42 Polish patients with sarcoidosis, 13 of which presented with Löfgren's syndrome (LS), and 94 control subjects. Dimorphisms at positions +2763 (A/G) and +2437 (C/T) of the HSP70‐hom gene were typed using amplification refractory mutation system and polymerase chain reaction–restriction fragment length polymorphism technique, respectively. A significant prevalence of the HSP(+2437)‐C allele and the HSP(+2437)‐CC homozygous genotype was observed in patients with sarcoidosis and in those presenting with LS as compared to controls (P < 0.001 in all comparisons made). A majority of HLA‐DRB1*03‐positive patients with LS were carrying both HSP(+2437)‐C and (+2763)‐G alleles, and the concomitant presence of these three genetic factors was more frequent among patients with LS as compared to patients without LS (0.54 vs. 0.17, P < 0.05) and controls (0.54 vs. 0.01, P < 0.001). The association of the HSP(+2437)‐C allele with sarcoidosis and LS appeared to be independent of the presence of DRB1*03, although this HLA specificity was associated with LS manifestation. The HSP(+2763)‐G allele was independently associated with neither sarcoidosis nor LS. However, this HSP(+2763)‐G allele was present with either DRB1*03 or HSP(+2437)‐C within the same haplotypes in the patients and this might explain the observed prevalence of DRB1*03, HSP(+2437)‐C and (+2763)‐G in patients with LS. In conclusion, HSP(+2437)‐C allele was found as a factor associating with susceptibility to sarcoidosis and LS.