Interleukin-1 receptor antagonist (IL-1RN) and interleukin-1B gene polymorphisms in Turkish patients with rheumatoid arthritis

OBJECTIVE: Interleukin 1 (IL-1) family is composed of two agonists, IL-1alpha and IL-1Beta and IL-1 receptor antagonist, IL-1Ra. The purpose of this study was to determine the relationship between polymorphisms of IL-1 receptor antagonist (IL-1RN), IL-1B promoter and IL-1B exon 5 genes and susceptibility to rheumatoid arthritis (RA) in Turkish population. METHODS: Polymerase chain reaction (PCR) was used to determine the genotype of the IL-1RN for 94 RA patients and 104 healthy controls. Genotyping of IL-1B polymorphisms at positions -511 (C/T) and +3953 (C/T) was detected by PCR followed restriction fragment length analysis. RESULTS: There was no significant difference in IL-1RN genotype and allele distributions between RA and the control groups. In addition, no significant association was observed in the allelic frequency (C or T) of IL-1B promoter (-511) between RA patients and the controls (P = 0,118), but the genotype distribution of 1/2 (C/T) at position -511 showed a significant difference (P = 0,038). Also, 2/2 genotype (T/T); (P = 0,028), and allele 2 (T) distribution (P = 0,011) of IL-1B (+3953) showed significant differences between RA patients and the control groups in the study population. CONCLUSION: These results imply that 2/2 (T/T) genotype or allele 2 (T) of IL-B (+3953) are susceptibility factors for RA in Turkey. Also, 1/2 genotype (C/T) of IL-1 -511 can play a protective role for RA.     

Genetic polymorphisms of interleukin-1beta in association with the development of alcoholic liver disease in Japanese patients

OBJECTIVE: Cytokine interleukin-1beta plays a central role in the inflammation process. Serum levels of IL-1beta are elevated in patients with alcoholic liver disease (ALD), especially in those with cirrhosis and alcoholic hepatitis. Recently, the presence of genetic polymorphisms of this cytokine was confirmed. The aim of this study was to determine whether IL-1beta polymorphisms are associated with the development of ALD. METHODS: We examined the frequency of two polymorphisms in the IL-1beta gene located in promoter -511 and exon 5 +3953 locus by restriction fragment length polymorphisms in 142 male patients with ALD, 30 heavy drinkers without ALD, and 218 healthy controls. RESULTS: The carriers of -511 IL-1beta allele 2 were present significantly more often in patients with alcoholic cirrhosis than in those with noncirrhotic ALD (p = 0.026), heavy drinkers without ALD (p = 0.001), and healthy controls (p = 0.032). The frequencies of allele 2 and heterozygotes of +3953 polymorphism were both significantly higher in heavy drinkers without ALD than in patients with ALD (allele, p = 0.030; genotype, p = 0.027) and healthy controls (allele, p = 0.047; genotype, p = 0.043). The haplotype, IL-1beta -511 allele 2/+3953 allele 1 was associated with the development of alcoholic cirrhosis (p < 0.05). CONCLUSIONS: These results suggest that IL-1beta polymorphisms may be related to the development of ALD in Japanese alcoholics.     

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.     

Lack of association of genetic polymorphisms in the interleukin-1beta, interleukin-1 receptor antagonist, interleukin-4, and interleukin-10 genes with risk of rheumatic heart disease in Taiwan Chinese

Inflammation and genetics may play a role in the pathogenesis of rheumatic heart disease (RHD). The aim of this study was to test whether interleukin (IL)-1beta, IL-1 receptor antagonist (IL-1Ra), IL-4, or IL-10 gene polymorphisms could be used as markers of susceptibility to or severity of RHD among the Chinese population in Taiwan. A group of 115 patients with RHD diagnosed by echocardiography, and 163 age- and sex-matched normal control subjects were studied. IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3, and IL-10 gene polymorphisms were identified by polymerase chain reaction-based restriction analysis. There was no significant difference in the distribution of genotypes and allelic frequencies between RHD cases and controls for IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3, and IL-10 gene polymorphisms. Further categorization of the RHD patients into mitral valve disease and combined valve disease subgroups also revealed no statistical difference in these gene polymorphisms when compared with controls. These findings suggest that the IL-1beta, IL-1Ra, IL-4, or IL-10 gene polymorphisms are not suitable genetic markers for RHD in Taiwan Chinese.     

Lack of association of genetic polymorphisms in the interleukin-1beta,interleukin-1 receptor antagonist,interleukin-4 and interleukin-10 genes with mitral valve prolapse in Taiwan Chinese

BACKGROUND AND AIMS OF THE STUDY: Inflammation and genetics may play a role in the pathogenesis of mitral valve prolapse (MVP). The study aim was to test whether interleukin-1beta (IL-1beta), IL-1 receptor antagonist (IL-1Ra), IL-4 or IL-10 gene polymorphisms could be used as markers of susceptibility or severity in MVP among the Chinese population in Taiwan. METHODS: A group of 100 patients with MVP diagnosed echocardiographically, and 103 age- and sex-matched normal control subjects was studied. IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3 and IL-10 gene polymorphisms were identified by polymerase chain reaction-based restriction analysis. RESULTS: There was no significant difference in the distribution of genotypes and allelic frequencies between MVP cases and controls for IL-1beta promoter, IL-1beta exon 5, IL-1Ra, IL-4 promoter, IL-4 intron 3 and IL-10 gene polymorphisms. Further categorization of MVP patients into mild and severe subgroups also revealed no statistical difference in these gene polymorphisms when compared with controls. CONCLUSION: These findings suggest that the IL-1beta, IL-1Ra, IL-4 or IL-10 gene polymorphisms are not suitable genetic markers of MVP in Taiwan Chinese.     

Interleukin 1alpha,interleukin 1beta and interleukin 1 receptor gene polymorphisms in psoriatic arthritis

OBJECTIVES: To investigate polymorphisms of interleukin (IL) 1alpha, IL-1beta and IL-1 receptor R1 genes in patients with psoriatic arthritis (PsA), their relationship to the age of onset of psoriasis and the pattern of joint involvement. METHODS: One hundred and forty well-characterized patients with PsA were studied. One hundred healthy controls were recruited from primary care. All were genotyped for single-nucleotide polymorphisms in the genes for IL-1alpha (position -889), IL-1beta (position +3953) and IL-1R1 (position +970). The frequencies of the respective variants were compared between patients and controls and in relation to age of onset of psoriasis, to clinical subsets of the disease and to the presence of erosions. RESULTS: All three polymorphisms were in Hardy-Weinberg equilibrium in both patients and controls. The frequency of IL-1alpha -889 CC homozygotes was significantly increased in PsA patients compared with normal controls [58 vs 40%, odds ratio (OR) 2.06, 95%, confidence interval (CI) 1.22-3.47]. The frequency of the IL-1alpha -889 C allele was significantly increased in PsA patients compared with controls (75 vs 65%, OR 1.65, 95% CI 1.11-2.45). In subset analysis there were no other significant differences in allelic frequencies for the IL-1alpha -889 C/T, IL-1beta +3953 C/T and IL-1R1 +970 C/T polymorphisms. CONCLUSIONS: The IL-1 gene complex may play a role in the development of PsA and/or psoriasis or act as a marker for other genes on chromosome 2q12 to 2q13.     

Susceptibility for and clinical manifestations of rheumatoid arthritis are associated with polymorphisms of the TNF-alpha, IL-1beta, and IL-1Ra genes

OBJECTIVE: To analyze the association of genetic polymorphisms of pro-inflammatory cytokines with rheumatoid arthritis (RA) in comparison with healthy controls from Northern Sweden and the potential contribution of these genetic variants for disease severity and development of cardiovascular complications. METHODS: Polymerase chain reaction amplification was used for analysis of TaqI restriction fragment length polymorphism (RFLP) of interleukin-1 beta (IL-1beta), variable tandem repeat polymorphism of IL-I receptor antagonist (IL-1Ra) gene and NcoI RFLP at position -308 of tumor necrosis factor-alpha (TNF-alpha) gene. One hundred and fifty-four patients with RA, 42 men and 112 women, were consecutively recruited into the study through the Department of Rheumatology. RESULTS: The allele A1 of TNF-alpha was more common in the patient group (p < 0.01; OR = 1.62). Patients having the genotype A1A2 seemed to develop more severe disease compared with patients with A1A1 genotype: they were younger at disease onset (p < 0.05), had a higher accumulated disease activity (p < 0.05) and worse functional class (p < 0.05). Patients with genotype A2A2 of IL- 1beta had higher accumulated disease activity score than patients with A1A1 and A1A2 (p < 0.05). The allelic combination Al IL-1beta/A2 IL-1Ra was less prevalent in RA patients who developed cardiovascular complications (p < 0.005; OR = 0.20). CONCLUSIONS: The Al allele of TNF-alpha associates with RA. Genotypes A1A2 of TNF-alpha and A2A2 of IL-1beta are associated with more severe disease. The allelic combination A1IL-1beta/A2 IL-1Ra is less often present in RA patients who developed cardiovascular complications.     

The interleukin-1 and interleukin-10 gene polymorphisms in primary sclerosing cholangitis: no associations with disease susceptibility/resistance

BACKGROUND/AIMS: Although primary sclerosing cholangitis is believed to be an autoimmune disorder, no tissue-specific auto-antibodies have yet been identified, and the strongest support for an autoimmune aetiology comes from HLA-association studies. Three different HLA haplotypes are associated with susceptibility to the disease and one with protection from it. These HLA haplotypes, however, do not account for all of the disease risk and genes outside the HLA region may also have a role in disease pathogenesis. The aim of this study was to investigate, for the first time, polymorphic genes/sites within the interleukin-1 and interleukin-10 genes in a large well-characterised group of patients. METHODS: Ninety-six patients and 96 control subjects were studied. A single base-exchange polymorphism at position +3953 in the first exon of the IL-1B gene, a penta-allelic repeat sequence in the IL-1 receptor antagonist gene (IL-1RN) and three single base-exchange polymorphisms at positions -592, -819 and -1082 in the IL-10 gene promoter were determined by standard PCR-based techniques. RESULTS: Overall, there was no significant difference in the distribution of any of the IL-1B, IL-1RN or IL-10 alleles or genes sequences comparing patients and controls. In addition, there was no difference when the patients were stratified for the presence and absence of the HLA DRB1*0301 (DR3) allele or concurrent inflammatory bowel disease. CONCLUSION: Neither the IL-1B +3953, IL-1RN microsatellites polymorphisms on chromosome 2q13 nor the IL-10 -592, -819, -1082 promoter gene polymorphisms on chromosome 1q31-32 are associated with susceptibility or resistance to primary sclerosing cholangitis.     

白细胞介素-1基因多态性与类风湿关节炎病情活动及骨代谢的相关性

目的 探讨IL－1α和β基因多态性与类风湿关节炎（RA）疾病活动性和骨代谢的相关以及IL－1基因多态性与RA优势基因（motif gene）之间的相关关系。方法 检测了65例RA 患者和60例非风湿病患者的IL－1等位基因分布。IL－1基因多态性分析采用PCR－RFLP方法,HLA－DR分型采用PCR－SSOP方法。Fisher's检验及方差分析被用于基因频率和携带率及临床统计。结果 IL－1α的频率和携带率在RA病人和对照组之间差异无显著性。在女性RA病人IL－1β纯合子等位基因2的出现频率更高,在男性RA病人中等位基因1的频率较高而等位基因2的携带率较低。IL－1β等位基因2携带率与C反应蛋白（CRP）、红细胞沉降率（ESR）、关节痛和骨质密度（BMD）呈相关,与尿脱氧吡啶／肌酐比值（Udpd/Crea）水平及维生素D3水平呈负相关。IL－1α等位基因1与CRP呈负相关,与类风湿因子（RF）和关节肿胀呈正相关。IL－1α等位基因2的出现伴随较高的ESR、健康质量评估积分（HAQ）,维生素D3水平和较低的RF滴度、肿胀关和（SJC）和BMD。HLA－DRB1 RA优势等位基因和IL－1β等位基因2的同时出现对RA 的一些临床参数并没有影响。结论 RA与IL－1基因多态性显著相关,特别是IL－1β等位基因2与病 情活动及骨密度增高直接。HLA－DRB1RA优势等位基因和IL－1β等位基因2的同时出现并不预示RA病情更严重。     

The −590 IL-4 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to evaluate the –590 IL-4 promoter polymorphism in patients with RA and its association with disease activity and severity. We enrolled 94 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the polymorphism at position –590 of the promoter of the IL-4 gene. The distribution of IL-4 genotypes in RA patients did not differ from control subjects. Nevertheless, the active form of RA was more frequently diagnosed in patients with T allele (genotypes CT and TT) as compared with homozygous CC patients. Moreover, in carriers of the T allele, parameters of disease activity (DAS 28 score, ESR, number of swollen and tender joints) were significantly increased. We suggest that the IL-4 –590 promoter polymorphism may be a genetic risk factor for RA severity.     

Donor interleukin 1 receptor antagonist genotype associated with acute graft-versus-host disease in human leucocyte antigen-matched sibling allogeneic transplants

Interleukin 1 (IL-1) is involved in various autoimmune and inflammatory diseases. IL-1 receptor antagonist (IL-1Ra) is the naturally occurring antagonist to IL-1alpha and -1beta. Polymorphisms of IL-1beta have been associated with variations in IL-1beta production (nucleotides +3953 and -511). A variable number tandem repeat (VNTR) polymorphism in the IL-1Ra gene has been associated (allele 2) with increased IL-1Ra production. We examined these polymorphisms in human leucocyte antigen (HLA)-matched allogeneic bone marrow transplant patients and donors. IL-1Ra VNTR (allele 2) in the donor genotype was more frequent with milder acute graft-versus-host disease (aGvHD) grades 0-II (29 out of 59 transplants) than severe GvHD grades III-IV (2 out of 18 transplants) (P = 0.0032). This association was confirmed in a subgroup with cyclosporine monotherapy prophylaxis: donor possession of allele 2 was again associated with milder aGvHD, grades 0-II (19 out of 38 transplants), than grades III-IV (1 out of 14) (P = 0.0042) transplants. No association was found between the IL-1beta -511 or IL-1beta +3953 polymorphism and severity of GvHD. Recipient IL-1Ra VNTR genotype (allele 2) showed a strong trend towards association with aGvHD severity (P = 0.0697). Thus, the donor genotype for the IL-1Ra polymorphism has an apparent protective role against acute GvHD following transplantation and may be an additional factor for individual risk assessment for complications, including GvHD, post transplant.     

Interleukin-10 promoter polymorphism in patients with rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory disease in which interleukin (IL)-10 plays an important role. There are, however, controversial reports that IL-10 promoter polymorphism may be an independent marker of susceptibility and severity of RA. The aim of the present study was to examine the IL-10 promoter polymorphism in patients with RA. We examined 95 patients with rheumatoid arthritis diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction amplification was used for analysis of the promoter polymorphism of the IL-10 gene. In RA patients, the prevalence of genotypes encoding high expression of IL-10 was observed. Nevertheless, there was no association between IL-10 genotypes and age at disease diagnosis, disease activity in a physicians global assessment, and joint and extra-articular involvement. There was also no correlation between IL-10 polymorphism and disease activity parameters—erythrocyte sedimentation rate, C-reactive protein, number of swollen and tender joints, and duration of morning stiffness. We suggest that IL-10 promoter polymorphism is not a genetic risk factor for RA activity.     

Lack of association of interleukin-1ß gene polymorphisms in Chinese patients with systemic lupus erythematosus

The purpose of this study was to examine whether interleukin-1beta (IL-1beta) (promoter and exon 5) gene polymorphisms were markers of susceptibility or clinical manifestation in Chinese patients with systemic lupus erythematosus (SLE). The study included 52 Chinese patients with SLE. In addition, 103 unrelated healthy individuals living in central Taiwan served as control subjects. From genomic DNA, polymorphisms of the gene for IL-1beta promoter and exon 5 were typed. Allelic frequencies were compared between SLE patients and control subjects. The relationship between allelic frequencies and clinical manifestations of SLE was evaluated. No significant differences were observed in the allelic frequencies of the IL-1beta promoter and IL-1beta exon 5 between patients with SLE and healthy control subjects. Additionally, we did not detect any association of IL-1beta promoter and the exon 5 genotype with the clinical and laboratory profiles in SLE patients. The results from the present study suggest that the polymorphisms of the IL-1beta promoter and IL-1beta exon 5 are not related to SLE patients in Taiwan.     

Cytokine gene polymorphisms: association with psoriatic arthritis susceptibility and severity

OBJECTIVE: To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA). METHODS: DNA was obtained from 147 PsA patients and 389 controls. Seven functional proinflammatory (interleukin-1beta [IL-1beta] +3953, IL-6 -174, tumor necrosis factor alpha [TNFalpha] -308, TNFbeta +252) and antiinflammatory (IL-10 -1082, IL-10 -592, IL-1 receptor antagonist [intron 2, 86 bp, variable-number tandem repeat]) gene polymorphisms were detected by polymerase chain reaction and restriction fragment length polymorphism assays. RESULTS: No significant difference in genotype frequencies was observed between the control and the PsA patient populations, and no association with Steinbrocker functional class, disease classification (polyarticular or oligoarticular), presence of spinal involvement, or age at PsA onset was observed. The presence of joint erosions was significantly associated with the TNFalpha -308 and TNFbeta +252 polymorphisms (P < 0.0001 and P = 0.0017, respectively). Frequencies of the TNFalpha -308 and TNFbeta +252 genotypes were also significantly different (P = 0.0078 and P = 0.0486, respectively) in a group of progressors (patients with early PsA in whom the number of joint erosions in the hands and feet increased over a median interval of 24 months) compared with a group of nonprogressors. Age at psoriasis onset was significantly associated with the TNFbeta +252 and TNFalpha -308 polymorphisms (P = 0.0003 and P = 0.0081, respectively). The TNFB2B2 and TNFalpha -308 AA genotypes were associated with the earliest mean ages at psoriasis onset. CONCLUSION: The TNFalpha -308 and TNFbeta +252 polymorphisms were significantly associated with age at psoriasis onset, presence of joint erosions in PsA, and progression of joint erosions in early PsA. TNF gene polymorphisms may be useful prognostic markers in PsA, and these results support the rationale for using anti-TNF treatment in patients with severe, progressive PsA.     

IL-6 promoter polymorphism in patients with rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is a chronic inflammatory disease in which cytokines play an important role. The aim of the present study was to examine the interleukin-6 (IL-6) -174 promoter polymorphism in patients with RA and its association with disease susceptibility and activity. METHODS: The study included 98 patients with RA diagnosed according to the criteria of the American College of Rheumatology. Polymerase chain reaction (PCR) amplification was used for analysis of the polymorphism at position -174 in the promoter of the IL-6 gene. RESULTS: The distribution of IL-6 genotypes in RA patients did not differ from that in control subjects. Nevertheless, in patients with a GG genotype the active form of RA was more frequently diagnosed compared with homozygous CC and GC patients. Moreover, in carriers of two G alleles the parameters of disease activity score (DAS28), erythrocyte sedimentation rate (ESR), number of swollen and tender joints] were significantly increased. CONCLUSION: We suggest that the IL-6 promoter polymorphism may be a genetic risk factor for RA activity.     

No association of polymorphisms of the CTLA-4 exon 1(+49) and promoter(-318) genes with rheumatoid arthritis in the Korean population

The aim of this study is to investigate the significance of the polymorphisms of the cytotoxic T lymphocyte associated antigen-4 (CTLA-4) exon 1(+49) and promoter(-318) genes in rheumatoid arthritis (RA). Polymerase chain reaction of genomic DNA-restriction fragment length polymorphism was used to determine genotypes of the CTLA-4 exon 1(+49) and promoter(-318) in 86 RA patients and 86 healthy control subjects. There was no significant difference in genotype, allele and phenotype frequencies of the CTLA-4 exon 1(+49) and promoter(-318) genes between RA patients and control subjects. There was no significant difference in age at onset, severity, functional class (> or = 3), physician global assessment, ESR, CRP or RF titer in patients with RA according to the CTLA-4 polymorphisms. Our data show that the polymorphisms within the CTLA-4 exon 1(+49) and promoter(-318) genes are not associated with susceptibility to RA and its clinical/serological manifestations in the Korean population.     

Association of polymorphisms of the tumour necrosis factor receptors I and II and rheumatoid arthritis

OBJECTIVE: To assess the role of polymorphisms of the tumour necrosis factor (TNF) receptors, TNF-RI (p55) and TNF-RII (p75) in the susceptibility to and severity of rheumatoid arthritis (RA) in Dutch patients. METHODS: A total of 319 consecutive RA patients, and a cohort of 90 female RA patients with detailed 12-yr follow-up were genotyped for the TNF-RI exon 1 (+36 A to G) and TNF-RII 3' UTR (+1690 T to C) polymorphisms. RESULTS: The frequencies of the TNF-RI and TNF-RII polymorphisms were determined in both patient groups and healthy controls, but no significant differences were found. To determine the relationship of these polymorphisms to disease severity, the extent of joint damage in the cohort of 90 female RA patients was analysed. No differences in severity were observed. CONCLUSION: These TNF-RI and TNF-RII polymorphisms were not found to be associated with susceptibility to or severity of RA in the Dutch population.     

Anaemia of chronic disease in AA amyloidosis is associated with allele 2 of the interleukin-1beta-511 promoter gene and raised levels of interleukin-1beta and interleukin-18

OBJECTIVE: In amyloid A (AA) amyloidosis the receptor for advanced glycation end products is a target for the circulating amyloid precursor protein (SAA) resulting in upregulation of the proinflammatory cytokine pathway. Besides inducing hepatic SAA synthesis the interleukin-1 cytokine family is involved in the regulation of haematopoiesis. We therefore studied the relationship between the circulating levels of interleukin-1beta (IL-1beta) and interleukin-18 (IL-18), a new member of the IL-1 complex, as well as polymorphisms within the IL-1 cluster with the occurrence of anaemia in patients with AA amyloidosis. DESIGN, SETTING AND SUBJECTS: The study included 54 adult patients with biopsy-proven reactive amyloidosis allocated into three groups on the basis of haemoglobin (Hb) level: group I included all patients with Hb < 110 g L(-1) (n = 16); group II patients (Hb > 110 g L(-1), n = 16) were selected to match group I patients with respect to sex, age, underlying disease (seropositive, erosive rheumatoid arthritis) and renal function; and group III patients (n = 38) represented all patients (unselected) with Hb > or = 110 g L(-1). Gene polymorphisms were studied by polymerase chain reaction restriction length assay and included the base exchange at position-889 of the IL-1alpha gene, the polymorphic region at position-511 and the polymorphic locus at exon 5, position +3954 of the IL-1beta gene, as well as the IL-1 receptor antagonist (IL-1Ra) exon 2 polymorphism caused by the 86-bp tandem repeats. Plasma IL-1beta, IL-1alpha, IL-18, IL-1 Ra, SAA, ferritin, soluble transferrin receptor and erythropoietin levels were studied by enzyme immunoassays. RESULTS: Circulating IL-beta and IL-18 were significantly raised in the anaemic patients with AA amyloidosis when compared with group II patients (matched, Hb > 110 g L(-1)) as well as group III patients (nonmatched, Hb > or = 110 g L(-1)). A significant inverse relationship was found between IL-1beta and haemoglobin levels, as well as between IL-18 and haemoglobin levels. The frequency of allele 2 (T) of the IL-1beta-511 promoter gene was significantly increased and that of allele 1 (C) decreased in anaemic amyloid patients (group I) when compared with group II and III patients. Circulating IL-1beta levels tended to be higher amongst the IL-1beta-511 allele 2 carriers than amongst the noncarriers, as well as amongst the anaemic amyloid patients filling all criteria of anaemia of chronic disease. CONCLUSION: The occurrence of anaemia in patients with AA amyloidosis is associated with allele 2 (T) of the IL-1beta-511 promoter gene and elevated levels of circulating IL-1beta and IL-18. In AA amyloidosis the raised cytokine levels may generate a vicious cycle leading to accelerated amyloidogenesis, suppression of erythropoiesis and aggravation of the underlying inflammatory disorder.     

Association of cytokine gene polymorphisms with bronchial asthma in Macedonians

Bronchial asthma is a multifactorial disease whereby both environmental and genetic factors contribute to its aetiology and/or clinical severity. The aim of this study was to examine the association of 22 cytokine gene polymorphism in the Macedonian population with bronchial asthma (BA). The sample of the population comprised of 301 normal unrelated individuals and 74 patients with BA. Cytokine genotyping was performed by PCR. Susceptible cytokine polymorphisms for BA for ten genotypes (IL-4 -1098/T:T, TNF-alpha -238/A:G, IL-4 -590/C:C, IL-2 +166/T:T, IL-2 -330/T:T, IL-10 -1082/G:G, IFNgamma utr5644/T:T, IL-10 -1082/A:A, IL-1beta +3962/T:T, IL-6 -174/G:G), six diplotypes, four haplotypes, and two alleles were found. Protective cytokine polymorphisms for BA for seven cytokine genotypes (IL-4 -1098/G:T, TNF- alpha -238/G:G, IL-2 -330/G:T, IL-4 -590/C:T, IFNgamma utr5644/A:T, IL-1beta +3962/C:T, IL-10 -1082/A:G), six cytokine diplotypes, four cytokine haplotypes, and four cytokine alleles were found. We concluded that several cytokine polymorphisms are protective, or susceptible associated with BA in population of Macedonians.     

Interleukin 1 beta (IL-1β) promoter C [-511] T polymorphism but not C [+3953] T polymorphism is associated with polycystic ovary syndrome

PCOS is a complex multifactorial disorder involving a number of genetic and environmental factors. One of the genetic factors that has been associated with PCOS is Interleukin 1 beta (IL-1β), is an important inflammatory cytokine that plays a regulatory role in both the body's immune and the inflammatory responses. All these responses appear to be are also affected in at least some women with PCOS. To investigate the possible association of polymorphisms of the IL-1β gene with the occurrence and clinical characteristics of PCOS, we evaluated two common polymorphisms of the IL-1β gene (promoter C [-511] T and exon 5 position [+3953]) in 200 Chinese women with PCOS and 177 healthy Chinese controls. We found the frequency of IL-1β C/C [-511] genotype in PCOS was significantly higher than that in the controls (χ(2) = 15.48, df = 1, P < 0.001 OR = 2.73 95% CI: 1.64-4.56 by genotype; χ(2) = 10.21, df = 1, P = 0.001 by allele). However in contrast, no association between genotype and relative allele frequencies was observed for the C [+3953] T polymorphism for Chinese women with PCOS when compared to that for a similar group of Chinese women without PCOS (P = 0.35).