HLA-DR4等位基因与类风湿关节炎疗效的关系

目的：探讨对类风湿关节炎（RA）联合使用改善病情抗风湿药（DMARDs）的疗效与易感HLA－DR4基因携带的关系。方法 测定RA患者HLA－DR4携带频率,并作病程、关节功能及红细胞沉降率（ESR）、C反应蛋白（CRP）、类风湿因子（RF）比较分析后,分别于阳性者及阴性者联用甲氨蝶呤（MTX）、柳氮磺吡啶（SASP）及氯奎（CQ）等DMARDs,并观察疗效。结果 HLA－DR4携带使患者ESR、CRP及RF值升高,使RA病情复杂化,给联合治疗带来困难,表现在控制症状及生化指标恢复正常值的时间上,HLA－DR4阳性组比HLA－DR4阴性组显著延迟;在RF值恢复正常方面,HLA－DR4阳性组比HLA－DR4阴性组病例显著减少,上述两方面与RA预后密切相关。在药物的副作用方面,两组差异无显著性。结论 HLA－DR4可作为判断RA治疗的重要预后指标。     

上海地区Ⅰ型自身免疫性肝炎与HLA-DRB1等位基因的相关性研究

目的 分析HLA－DRB1等位基因与上海地区I型自身免疫性肝炎（AIH）的相关性，探讨AIH的遗传易感背景。方法 采用序列特异性多聚酶链反应（PCR－SSP），对32例I型AIH患者和48例健康对照者进行HLA－DRB1等位基因及有关基因亚型的分析。结果 HLA－DR4基因频率在I型AIH患者中较健康对照组显著增高[46.9%与20.8%；相对危险度（RR）＝3．35，χ^2=5.99,P=0.014]。其他等位基因在两组间差异无显著性。进一步对HLA－DR4等位基因亚型的分析表明，I型AIH患者组DRB1^*0405的基因频率较健康对照组有增加趋势（21．9％与6．3％，χ^2=4.23,P=0.04，但Pc=0.08)。HLA－DRβ分子的第3等位基因高变区第71位精氨酸残基的频率在I型AHI患者中显著增高（46.9%与18.8%,χ^2=7.14,P=0.008)。结论 上海地区I型AIH的发病与HLA－DR4以及HLA－DRB1第3高变区DR7位精氨酸残基相关。     

HLA—DRB1、DQB1基因多态性与流行性出血热的相关性

目的从基因水平探讨HLA—DRB1、DQB1等位基因多态性与流行性出血热的相关性,以阐述其免疫遗传学特征。方法应用序列特异性引物聚合酶链反应技术检测流行性出血热患者和正常对照组各50例的HLA—DRB1、DQB1等位基因。结果流行性出血热患者与正常对照组比较,HLA—DRB1＊16等位基因分布频率明显增高（Pc=0．0106）,两组间其余HLA-DRB1、-DQB1等位基因分布频率差异无统计学意义（Pc〉0．05）。结论HLA-DRB1＊16等位基因与流行性出血热呈正相关,可能为流行性出血热易感基因之一。     

HLA—DRB和ACE基因与肺结核的相关性分析

目的 探讨人类白细胞抗原（HLA）-DRB基因和血管紧张素转换酶（ACE）基因多态性与肺结核的相关性。方法采用聚合酶链反应-序列特异性引物法（PCR—SSP）对肺结核组和健康对照组进行HLA—DRB和ACE基因分型。结果肺结核组HLA—DRB1＊15等位基因的频率显著高于对照组（P〈O．05）；复治和耐药肺结核组ACE基因的I／D基因型频率显著高于初治和无耐药组（P〈O．05）。结论HLA—DRB1＊15等位基因及ACE基因的I／D基因型与肺结核密切相关。     

人类白细胞抗原-DRB1与胃腺癌及其临床特征和幽门螺杆菌感染的相关性

目的：探讨人类白细胞抗原（HLA）－DRB1等位基因与胃腺癌及其临床特征和幽门螺杆菌（Hp)感染的关联性，方法：运用序列特异性引物聚 合酶链反应和等基因序列分析技术，检测无亲缘关系湖北省汉族健康人136例，胃癌组63例的HLA－DRB1基因，内镜活检，Giemsa染色和（或）外周血ELISA检查胃黏膜Hp感染情况，SAS软件数据处理，结果：HLA－DRB10901，12等位基因均与湖北省汉族人胃腺癌呈正相关，HLA－DRB115等位基因同呈负相关，携带及非携事寂述各等位基因患者，分别就其临床特征，包括平均患病年龄，性别比，肿瘤原发部位，TNM分期，肿瘤细胞分化程度以及Hp感染率等情况比较，差异均无显著性，结论：HLA－DRB10901，12等位基因均与湖北省汉族胃腺癌呈正相关，而LA－DRB115则呈负相关，上述各相关的HLA－DRB1等位基因与胃腺癌患者患病年龄，性别，TMN分期，肿瘤细胞分化程度无关，Hp感染虽为胃癌重要的致病因素，但并不是HLA-DRB1等位基因通过增加Hp感染危险性，而影响胃癌的遗传易感性。     

GD药物引起粒细胞减少与等位基因的关系

采用多聚酶链式反应-序列特异引物（per—ssp）方法检测65例GD病人抗甲状腺药物引起粒细胞减少（1）组，65例GD病人并发粒细胞减少（2）组，65例非GD病人粒细胞减少（3）组，65例正常参照人群（4）组的HLA—DRB1＊08032 DRB1＊1501的等位基因频率。结果1：（1）组HLA—DRB1＊08032 DRB1＊1501的基因频率高于（2）组（P〈0．05）。2：（1）组HLA—DRB1＊08032 DRB1＊1501的基因频率明显高于（3）组（4）组，（P〈0．01）。3：（2）组HLA—DRB1＊08032 DRB1＊1501的基因频率高于（4）组（P〈0．05）。结论：GD病人应用抗甲状腺药物引起粒细胞减少与HLA—DRB1＊08032 DRB1＊1501等位基因频率增加有关。     

雌激素受体基因多态性与女性类风湿关节炎相关性的研究

目的分析雌激素受体(ER)基因XbaⅠ和PvuⅡ酶切多态性在女性类风湿关节炎(RA)中的分布,探讨其与人类白细胞抗原(HLA)-DRβ1*04基因亚型、类风湿因子(RF)以及RA患者临床表现的关系。方法采用聚合酶链反应-限制性片断长度多态性(PCR-RFLP)技术,对81例女性RA患者和146名女性正常对照者的ER基因(XbaⅠ、PvuⅡ位点)进行分型,并计算基因分布频率。分析患者的HLA-DRβ1*04基因亚型、RF以及临床表现与ER基因多态性之间的关系。结果女性RA患者的ER基因X、P基因频率均明显高于健康对照组,ER基因的XX和PP基因亚型的阳性率分别高于正常对照组(P<0.05)。而RA患者的xx基因亚型的阳性率明显低于健康对照组(P<0.05)。RA患者XXPP基因型的阳性率明显高于健康对照组,而xxpp基因型的阳性率明显低于健康对照组(P<0.05)。携带PP基因型的RA患者HLA-DRβ1*04基因亚型的阳性率明显升高(P<0.05)。ER基因中pp基因型、XXpp和xxPP基因型的患者关节受累数明显增高(P<0.05)。结论女性RA患者ER基因的X和P的基因频率表达明显增高。ER基因酶切多态性分析中,XX、PP及XXPP基因型可能与女性RA的易感性相关。PP基因型可能与HLA-DRβ1*04基因有一定的相关性,pp基因型、XXpp和xxPP基因型可能与RA关节病变的程度相关。     

上海地区I型自身免疫性肝炎与HLA-DRB1等位基因的相关性研究

目的 分析 HLA—DRB1等位基因与上海地区I型自身免疫性肝炎（AIH）的相关性,探讨 AIH的遗传易感背景。方法 采用序列特异性多聚酶链反应（PCR—SSP）,对32例I型AIH患者和48例健康对照者进行HLA—DRB1等位基因及有关基因亚型的分析。结果HLA—DR4基因频率在I型AIH患者中较健康对照组显著增高[46.9％与20.8％;相对危险度（RR）=3.35,x2=5.99,P=0.014]。其他等位基因在两组间差异无显著性。进一步对HLA-DR4等位基因亚型的分析表明,I型AIH患者组DRB1＊0405的基因频率较健康对照组有增加趋势（21.9％与6.3％,x2=4.23,P=0.04,但 Pc=0.08）。HLA—DRβ分子的第3等位基因高变区第71位精氨酸残基的频率在I型AIH患者中显著增高（46.9％与 18.8％,x2=7.14,P=0.008）。结论 上海地区I型 AIH的发病与HLA—DR4以及HLA—DRB1第3高变区DR71位精氨酸残基相关。     

HLA—DRB和ACE基因与肺结核的相关性分析

目的探讨人类白细胞抗原（HL气）-DRB基因和血管紧张素转换酶（ACE）基因多态性与肺结核的相关性。方法采用聚合酶链反应-序列特异性引物法（PCR—SSP）对肺结核组和健康对照组进行HLA-DRB和ACE基因分型。结果肺结核组HLA—DRB1＊15等位基因的频率显著高于对照组（P〈0．05）；复治和耐药肺结核组ACE基因的I／D基因型频率显著高于初治和无耐药组（P〈0．05）。结论HLA—DRB1＊15等位基因及ACE基因的I／D基因型与肺结核密切相关。     

STAT4基因多态性与类风湿关节炎病情活动的关系

目的研究STAT4基因多态性与唐山地区类风湿关节炎（RA）患者病情活动度和疾病严重度的相关性。方法采用PCR-LDR法检测RA患者的STAT4基因型,记录其年龄、性别、病程、双手/双腕关节X线分期,检测血沉（ESR）,计算DAS28评分。结果 STAT4 rs7574865位点T等位基因为RA发病的危险基因;T等位基因与患者的年龄、性别、病程、双手/双腕关节X线分期、ESR及DAS28评分均无相关性（P均〉0.05）。结论 STAT4基因多态性与唐山地区汉族人群RA病情活动度及疾病严重度不相关。     

HLA Class ii sequence polymorphisms and susceptibility to rheumatoid arthritis in greeks. the hla–drβ shared-epitope hypothesis accounts for the disease in only a minority of greek patients

Objective. In Northern Europeans, rheumatoid arthritis (RA) is strongly associated with a relatively conserved pentapeptide sequence of HLA–DRβ found notably in the HLA–DR4 subtypes Dw4 and Dw14 and in DR1. A previous serologic study of HLA class II polymorphism in a Greek population with RA failed to show significant associations with any antigen. Methods. We characterized HLA–DRB polymorphisms in Greek patients with RA and in control subjects by restriction fragment length polymorphism analysis. Allelic DRB subtypes were examined by polymerase chain reaction amplification and oligonucleotide hybridization. Results. DNA analysis in the RA patients showed that although individual HLA–DR allelic associations were weak, a relatively conserved HLA–DRβ motif was significantly associated with RA in this population of Greek patients. The third hypervariable region amino acid sequences QRRAA, QKRAA, or RRRAA were found in the HLA–DRβ1 of 43.5% of the RA patients versus 15.5% of the controls (unconnected P = 0.00004). Conclusion. Sequences shown to influence susceptibility to RA in patients in the UK also play a role in patients in Greece. However, 57% of Greek patients lack the putative HLA–DRβ motif, which suggests that considerable immunogenetic heterogeneity underlies disease susceptibility in this population.     

Interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in rheumatoid arthritis

The purpose of this study was to evaluate if IL-1beta (IL-1beta promoter and IL-1beta exon 5) and IL-1receptor antagonist (IL-1Ra) gene polymorphisms act as markers of susceptibility to or severity of RA. The study included 104 RA patients and 103 normal controls. No significant difference was observed in the cytokine allelic frequencies of IL-1beta promoter and IL-1beta exon 5 between patients with RA and healthy controls. In addition, there was no significant association in the cytokine carriage rates of I and II allele of IL-1Ra between RA patients and healthy controls. In contrast, the IV allele of IL-1Ra was significantly increased in RA patients with low inflammatory activity (P=0.03). This study indicated that allelic frequency and carriage rate of IL-1beta (IL-1beta promoter and IL-1beta exon 5) and IL-1Ra (I and II allele) do not differ significantly between normal controls and RA patients in Taiwan. However, the carriage rate of IV allele of IL-1Ra was high in the RA patients with low inflammatory activity.     

Genetic markers may predict disease behavior in patients with ulcerative colitis

BACKGROUND & AIMS: Recent studies have suggested that HLA DRB1*0103 and allele 2 of the interleukin 1 receptor antagonist (IL-1RA) gene predict severe and extensive ulcerative colitis, respectively. The aim of this study was to test these hypotheses in patients undergoing surgery for their colitis. METHODS: HLA DRB1 and DQB1 genotyping was performed in 99 patients and 472 controls. Genotyping for polymorphisms of genes encoding tumor necrosis factor alpha and IL-1RA was performed in 107 patients and 89 controls. Measurement of antineutrophil cytoplasmic antibody (ANCA) was performed in 72 patients and 58 healthy subjects by fixed neutrophil enzyme-linked immunosorbent assay and indirect immunofluorescence. RESULTS: The DRB1*0103 allele was increased in patients (14.1% vs. 3.2% in controls; P < 1 x 10[-5]). This association was greatest in patients with extensive disease (15.8%; P < 0.0001) or extraintestinal manifestations (22.8%; P < 0.0001): mouth ulcers (25.8%; P < 0.0001), arthritis (27.2%; P < 0.0001), and uveitis (35.7%; P < 0.0001). The DRB1*04 alleles were reduced in patients (P = 0.005). Differences were noted between extensive and distal disease in the frequency of allele 2 of IL-1RA (10.9% in distal vs. 28.6% in extensive; P = 0.01) and allele 2 homozygosity. ANCA was detected in 76.4% of patients. Carriage of IL-1RA allele 2 and tumor necrosis factor 2 allele was increased in ANCA-positive patients. CONCLUSIONS: Genetic markers may predict disease behavior in ulcerative colitis. (Gastroenterology 1997 Jun;112(6):1845-53)     

Association of transforming growth factor beta1 and tumor necrosis factor alpha polymorphisms with anti-SSB/La antibody secretion in patients with primary Sjögren's syndrome

OBJECTIVE: To determine whether cytokine gene polymorphisms of interferon-gamma (IFNgamma), interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNFalpha), and transforming growth factor beta1 (TGFbeta1) predispose subjects to the development of primary Sj?gren's syndrome (SS). METHODS: Single-base-exchange cytokine gene polymorphisms were analyzed in 129 French patients with primary SS who fulfilled the American-European Consensus Group criteria, as well as in 96 unrelated healthy subjects. RESULTS: The frequency of the TNF-308A (TNF2) allele was significantly higher in the SS patients (26% versus 11%). This TNF2 association was restricted to patients with anti-SSB (37% versus 11% in controls). Stratification did not reveal an independent effect of TNF2 and HLA-DRB1*03 on disease or on anti-SSB antibody secretion. The frequency of allele C at codon 10 of TGFbeta1 was strongly increased in the subgroup of patients with anti-SSB; this allele acted synergistically with DRB1*03 to predispose patients to the secretion of anti-SSB. The IL-10 GCC haplotype carrier rate was significantly higher in SS patients than in controls (67% versus 48%), but the IL-10 allele and genotype frequencies were not significantly different. No association was found between IL-6 or IFNgamma polymorphisms and primary SS. CONCLUSION: TNF2 was associated with anti-SSB antibody secretion, although this association was not independent of the association with DRB1*03. Allele C at codon 10 of TGFbeta1 was found to act synergistically with DRB1*03 in predisposing patients to the secretion of anti-SSB. These results therefore suggest that most of the known genetic predisposition to primary SS might concern the pattern of autoantibody diversification.     

IL-4 VNTR gene polymorphism in chronic polyarthritis. The rare allele is associated with protection against destruction

OBJECTIVE: To evaluate the occurrence of variants of the interleukin 4 (IL-4) and IL-4 receptor (IL-4R) genes in patients with rheumatoid arthritis (RA) and their possible contribution to joint destruction. METHODS: Allelic frequencies for polymorphisms in the IL-4 [variable number of tandem repeat (VNTR) polymorphism in intron 3] and IL-4 receptor alpha chain (transition at nucleotide 1902) genes were assessed in 335 RA patients and 104 controls. Clinical indices of disease activity, disability and joint destruction and plasma levels of IL-1beta, IL-1Ra and sCD23 were assessed to evaluate a possible functional effect. RESULTS: Carriage of the rare IL-4(2) allele was higher in patients with non-destructive RA (40%) than in those with destructive RA (22.3%; odds ratio = 1.9, 95% confidence interval 1. 1-3.5, P = 0.0006) and in controls (26%, P = 0.002). Patients positive for this rare allele had significantly less joint destruction, assessed by the Larsen wrist index (P = 0.004) and a lower erythrocyte sedimentation rate (P = 0.04). A significantly higher carriage rate of IL-4(2) was seen in HLA-DR4/DR1(-) patients with non-destructive RA than in those with destructive RA. The IL-4 receptor polymorphism was not over-represented. Plasma levels of IL-1beta, IL-1Ra and sCD23, known to be modified by IL-4, were not different in individuals having different alleles. CONCLUSION: This IL-4 VNTR gene polymorphism may be a protective factor for severe joint destruction in RA that could be used as a prognostic marker early in the course of the disease.     

Predictive value of interleukin 1 gene polymorphisms for surgery

OBJECTIVES: To determine the influence of interleukin 1alpha (IL1alpha), IL1beta, and IL1 receptor antagonist gene polymorphisms on disease outcome as assessed by the need for major joint surgery within 15 years of diagnosis. PATIENTS AND METHODS: 50 patients with rheumatoid arthritis (RA) who required major joint surgery (hip, knee, or shoulder arthroplasty) within a 15 year period of disease diagnosis and 50 patients with RA with disease duration greater than 15 years and no major surgery were recruited together with 66 normal west of Scotland controls. Genomic DNA and polymerase chain reaction were used to determine polymorphisms in the genes for IL1alpha, IL1beta, and IL1 receptor antagonist. For all patients with RA recruited to the study, HLA-DR beta1 gene status was recorded as was the erythrocyte sedimentation rate (ESR) at the first ever clinic visit. RESULTS: No difference in the allele frequencies or genotypes of the IL1alpha and IL1 receptor antagonist gene polymorphisms was found between the controls and patients with RA, with or without previous surgery. IL1beta allele 2 was overrepresented in patients with RA who had undergone surgery compared with patients who had not (40% v 27%, chi(2)=4, 1df, p=0.04). ESR at the first ever clinic visit was significantly higher in those carrying allele 2 (36 mm/1st h v 22 mm/1st h, p=0.04). When patients, with or without previous surgery, who did not carry two disease associated HLA-DR beta1 alleles were compared, an increase in allele 2 was observed in the surgery cohort (42% v 25%, chi(2)=4.8, 1df, p=0.03). CONCLUSIONS: Patients who require major joint surgery were found to carry the IL1beta allele 2 more often than expected. Patients with this allele also had a higher initial ESR. This may be useful in predicting early surgery in patients who do not carry two disease associated HLA-DR beta1 alleles. Although these findings are interesting, further functional and epidemiological studies to confirm these observations are required.     

Prospective analysis of the impact of HLA-DR and -DQ on joint destruction in recent-onset rheumatoid arthritis

OBJECTIVE: To evaluate the differential impact of HLA-DR and -DQ on the progression of erosive disease in the clinical course of early rheumatoid arthritis (RA). METHODS: HLA genotyping for HLA-DR and -DQ was carried out in a prospective study of 87 patients with early RA. The progression of erosive disease was assessed by radiological scores over a period of 2 yr in all patients and over 4 yr in 77 patients. The impact of HLA markers was evaluated by univariate comparisons and by multiple logistic regression analyses. RESULTS: Patients expressing the RA-associated shared epitope (SE) on a DRB1*01-positive or, most prominently, on a DRB1*04-positive allele had higher Larsen scores at all time-points analysed when compared with SE-negative patients. A similar impact on radiological progression was seen for the RA-predisposing DQ3, but not for DQ5 heterodimers. In the presence or absence of the DRB1 SE, no additional effects could be discerned for RA-associated DQ molecules. The presence of a DERAA-positive DRB1 allele was associated with a slower pace of joint destruction. While gene dosage effects were seen for SE compound homozygosity, no effect for DQ3 homozygosity could be discerned. CONCLUSION: Although a significant influence of HLA-DQ3 heterodimers on the progression of erosive joint destruction was seen, the analysis of the HLA-DQ locus did not add additional information over the study of HLA-DR including the determination of the SE and the DERAA motif in order to predict the development of severe progressive joint destruction.     

Identification of a genetic risk factor for systemic juvenile rheumatoid arthritis in the 5'-flanking region of the TNFalpha gene and HLA genes

OBJECTIVE: To study polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor alpha (TNFalpha) gene and in the coding regions of HLA class I and class II genes, in order to better understand the genetic background of juvenile rheumatoid arthritis (JRA). METHODS: One hundred eleven Japanese JRA patients (50 with systemic disease, 29 with pauciarticular disease, and 32 with polyarticular disease) and 575 healthy Japanese subjects were examined for the allele frequencies of the TNFalpha, HLA-A, and HLA class II (DRB1, DRB3, DRB4, DRB5, DQA1, DQB1, DPA1, and DPB1) genes, by DNA typing using the polymerase chain reaction-sequence-specific oligonucleotide probe method. RESULTS: The frequencies of the polymorphic allele at positions -1,031 (T to C substitution, termed -1,031C), -863 (C to A, termed -863A), and -857 (C to T, termed -857T) of the TNFalpha gene in patients with systemic JRA, but not in those with polyarticular or pauciarticular JRA, were significantly higher than in the healthy controls. The allele frequencies of DRB1*0405 and DQB1*0401 in systemic JRA, but not in the other JRA types, were significantly higher than in controls. Linkage analysis showed that the presence of both the TNFalpha -857T allele and DRB1*0405 yielded a significantly increased odds ratio (3.84), while the presence of only 1 of them did not yield a high odds ratio (0.87 and 1.58). CONCLUSION: The -1,031C/-863A allele and the -857T allele of the TNFalpha gene, both of which are related to high production of tumor necrosis factor alpha, are associated with systemic JRA. The -857T allele may enhance the effect of the DRB1*0405/DQB1*0401 haplotype in predisposing to development of systemic JRA.     

Hla–drb1 alleles in polymyalgia rheumatica,giant cell arteritis,and rheumatoid arthritis

Objective. Immunogenetic analysis has demonstrated that giant cell arteritis (GCA) and rheumatoid arthritis (RA) are associated with 2 different domains of the HLA–DR4 molecule. The present study was undertaken to evaluate whether polymyalgia rheumatica (PMR) immunogenetically resembles GCA or RA and to determine whether expression of HLA-DRB1 alleles can be used to detect heterogeneity among PMR patients. Methods. Forty-six patients with PMR, 52 with GCA, 122 with seropositive RA, and 72 normal individuals were genotyped for HLA-DRB1 alleles by allele-specific amplification and subsequent oligonucleotide hybridization. Results. The HLA-DRB1^*04 allele was the most frequent among PMR patients (67%). While the expression of allelic variants of the HLA-DR4 family was restricted to HLA-DRB1^*0401 and ^*0404/8 in RA patients, all HLA–DRB1^*04 alleles, including B1^*0402 and B1^*0403, were represented in the PMR group. The distribution of HLA–DRB1 alleles among HLA–DRB1^*04 negative patients was similar in those with PMR and those with GCA, and could be distinguished from that in RA patients. In particular, HLA–DRB1^*01 alleles, which were found in most HLA–DRB1^*04 negative RA patients, were underrepresented in patients with PMR and GCA. Conclusion. The distribution of HLA–DRB1 alleles in PMR resembles that found in GCA. PMR and GCA share the associated sequence polymorphism encoded by the second hypervariable region (HVR) of the HLA–DRB1 gene. The HLA–DRB1 association of PMR and GCA can be distinguished from that of RA, which is linked to a sequence motif in the third HVR of DRB1 alleles. The differential role of distinct domains on HLA-DR molecules suggests that multiple biologic functions are regulated by these molecules and that they contribute differently to disease mechanisms. The similarities in the distribution of HLA–DRB1 alleles in PMR and GCA indicates that HLA–DRB1 alleles are not predictive for progression of PMR to the vasculitic lesions that are pathognomonic for GCA.     

The interleukin-1 family gene polymorphisms and Graves’ disease

Genetic factors, including cytokine gene polymorphisms, are potential contributors to the pathogenesis of the Graves’ disease (GD). We attempted in this study to determine the association between GD and the following polymorphisms in the interleukin-1 (IL-1) family genes: IL-1α (−889C/T), IL-1ß (−511C/T), IL-1ß (+3962C/T), IL-1R (Pst-1 1970C/T) and IL-1RA (Mspa-I 11100 C/T). We studied 107 patients with an established diagnosis of GD and 140 healthy controls. Cytokine typing was performed by the polymerase chain reaction with sequence-specific primers assay. Genotype distributions among patients were in Hardy-Weinberg equilibrium for all polymorphisms. The frequency of the IL-1α −889T allele was significantly higher in patients than in controls (51.9% vs. 31.6%, OR = 2.33, 95% CI = 1.61-3.38; p < 0.0001). The IL-1RA Msp-I 11100C allele was significantly more frequent in patients than in controls (50.0% vs. 22.9%, OR = 3.38, 95% CI = 2.29-4.97, p < 0.0001). No significant associations were found for other polymorphisms. Although the IL-1 family has well-known roles in GD pathogenesis, the contributions of their genetic variations to the disease are unclear. In this study, we documented a highly significant association between GD and polymorphism in IL-1α and IL-1RA genes. Further studies in other populations are necessary to confirm our results.