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Biomedical subjects

G W Duff

Publications and source records attributed to G W Duff.

At least 37 records · Page 2Linked to original sources
PubMed2000

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.

Alleles↗
PubMed2000

Interleukin-1 genetic association with periodontitis in clinical practice.

BACKGROUND: Periodontitis is a bacterial disease modified by multiple risk factors. The pro-inflammatory cytokine interleukin- (IL-1) is a key regulator of the host responses to microbial infection and a major modulator of extracellular matrix catabolism and bone resorption. It has been reported that variations in the IL-1 gene cluster on chromosome 2 are associated with increased susceptibility to severe adult periodontitis. METHODS: The present study evaluated the association between a composite IL-1 genotype, including allele 2 at each of two loci (IL-1A +4845 plus IL- B +3954), and a broad spectrum of periodontally healthy to diseased patients in a population that is typically encountered in a dental practice setting. Ninety patients, non-smokers or former smokers with less than 10 pack-year (pk/yr) history, were recruited from a private dental practice. The major outcome variable was bone loss determined by computerized linear measurements of radiographs. Genotypes were analyzed from finger-stick blood samples using previously reported methods. RESULTS: Multivariate logistic regression models demonstrated that patient age, former smoking history, and the IL-1 genotype were significantly associated with severity of adult periodontitis. For non-smokers or former light smokers (<5 pk/yr), IL-1 genotype positives were at increased odds ratio of having moderate to severe periodontal disease of 3.75 (95% CI: 1.04-13.50) to 5.27 (95% CI: 1.23-22.70), depending on ethnicity, compared to IL-1 genotype negatives. Former moderate smokers (>5 pk/yr and <10 pk/yr) who were IL-1 genotype negative were at increased odds ratio of having moderate to severe periodontal disease of 7.43 (95% CI: 1.20-46.20) compared to non-smokers or former light smokers who were IL-1 genotype negative. In addition, past smoking history was also a significant effect modifier as demonstrated by the statistically significant interaction between past smoking history status and IL-1 genotype status. CONCLUSIONS: This study demonstrates that the composite IL-1 genotype is significantly associated with the severity of adult periodontitis. It also confirmed that both IL-1 genotyping and smoking history provide objective risk factors for periodontal disease in a private practice environment.

Adult↗
PubMed2000

Low prevalence of a periodontitis-associated interleukin-1 composite genotype in individuals of Chinese heritage.

BACKGROUND: Polymorphisms in the interleukin-1 (IL-1) gene cluster have been associated with an increased risk of developing certain diseases. A specific composite genotype of IL-1A and IL-1B polymorphisms, consisting of allele 2 of both IL-1A +4845 and IL-1B +3954 (formerly +3953) has been associated with an increased risk of severe adult periodontitis. Approximately 30% of the European population carry this genotype. The prevalence of the above IL-1A and IL-1B composite genotype in populations of different ethnic origins is unknown. Therefore, the primary aim of this study was to determine the prevalence of the IL-1 composite genotype in individuals of Chinese heritage, since epidemiologic studies indicate that periodontitis is widespread among ethnic Chinese. An additional aim was to evaluate if there was an association between the composite genotype and the severity of periodontal disease. METHODS: A convenience sample of 300 volunteers of Chinese heritage (ages 21 to 69 years) received a periodontal examination including full-mouth clinical attachment loss measurements, probing depths, plaque index scores, and bleeding on probing. Blood was collected from a fingerstick and placed on a blotting paper card. The blood samples were analyzed for IL-1A +4845 and IL-1B +3954 polymorphisms using polymerase chain reaction (PCR)-based methods. RESULTS: Only 7 of the 300 subjects (2.3%) carried the composite IL- 1 genotype consisting of allele 2 of both IL-1A +4845 and IL-1B +3954. Allele 2 of the IL-1A +4845 polymorphism was carried by 17.0% (51/300) of the subjects; of these, only 2 were homozygous. Allele 2 of the IL-1B +3954 polymorphism was much rarer with only 3.3% (10/300) of the study population carrying this marker. All of the people who carried the IL-1B polymorphism were heterozygous. Too few of the subjects were positive for the IL-1 composite genotype to establish any relationship with the susceptibility to periodontitis. CONCLUSIONS: It was concluded that the prevalences of both IL-1A and IL-1B polymorphisms are dramatically lower in Chinese than those reported for Europeans. Findings from this study bring into question the usefulness of the composite genotype of allele 2 of both IL-1A +4845 and IL-1B +3954 as a method for determining the susceptibility of Chinese patients to adult periodontitis.

Adult↗
PubMed1999

Interleukin-1 receptor antagonist gene polymorphism and coronary artery disease.

BACKGROUND: Cytokine gene variations are contributory factors in inflammatory pathology. Allele frequencies of interleukin (IL)-1 cluster genes [IL-1A(-889), IL-1B(-511), IL-1B(+3953), IL-1RN Intron 2 VNTR] and tissue necrosis factor (TNF)-alpha gene [TNFA(-308)] were measured in healthy blood donors (healthy control subjects), patients with angiographically normal coronary arteries (patient control subjects), single-vessel coronary disease (SVD), and those with multivessel coronary disease (MVD). METHODS AND RESULTS: Five hundred fifty-six patients attending for coronary angiography in Sheffield were studied: 130 patient control subjects, 98 SVD, and 328 MVD. Significant associations were tested in an independent population (London) of 350: 57 SVD, 191 MVD, and 102 control subjects. IL-1RN*2 frequency in Sheffield patient control subjects was the same as in 827 healthy control subjects. IL-1RN*2 was significantly overrepresented in Sheffield SVD patients (34% vs 23% in patient control subjects); IL-1RN*2 homozygotes in the SVD population (chi2 carriage=8.490, 1 df, P=0.0036). This effect was present though not quite significant in the London population (P=0. 0603). A summary trend test of the IL-1RN SVD genotype data for Sheffield and London showed a significant association with *2 (P=0. 0024). No significant effect of genotype at IL-1RN was observed in the Sheffield or London MVD populations. Genotype distribution analysis comparing the SVD and MVD populations at IL-1RN showed a highly significant trend (P=0.0007) with the use of pooled data. No significant associations were seen for the other polymorphisms. CONCLUSIONS: IL-1RN*2 was significantly associated with SVD. A difference in genetic association between SVD and MVD was also apparent.

Coronary Disease↗
PubMed1999

Primary biliary cirrhosis shows association with genetic polymorphism of tumour necrosis factor alpha promoter region.

BACKGROUND/AIMS: Primary biliary cirrhosis is an autoimmune disease in which increased prevalence in first-degree relatives and an association with HLA DR8 suggest a genetic background. TNFalpha is a mediator of inflammation and immunity, and is implicated in the pathogenesis of primary biliary cirrhosis, ex vivo studies having shown reduced production of TNFalpha by lymphocytes from patients. Our group has previously described a biallelic promoter-region polymorphism of the TNFA gene at position -308, and demonstrated that the rare allele, TNF*2, has increased promoter function compared with the common allele, TNF*1. A further biallelic base change has been described in the TNFA gene at -238. We conducted a case-control study to assess association of these gene polymorphisms with primary biliary cirrhosis. METHODS: Ninety-one patients and 213 controls were genotyped for both TNFA loci using restriction fragment length polymorphism analysis of PCR products. RESULTS: The high production TNFA-308*2 allele was significantly under-represented among subjects with primary biliary cirrhosis (27.5% PBC, 41.6% controls, p=0.02, pc=0.04, OR for carriage of TNF*1/*1 genotype=1.89, CI=1.10-3.32). No association was shown with the TNFA -238 polymorphism. CONCLUSION: Primary biliary cirrhosis is associated with reduced carriage of TNF*2. This is in keeping with a protective role of TNFalpha against the disease.

Adult↗
PubMed1999

Novel genetic association between the corneodesmosin (MHC S) gene and susceptibility to psoriasis.

Psoriasis is an inflammatory skin disease of unknown origin, but with a clear genetic component. The strongest genetic association has been found with the major histocompatibility complex (MHC) region, and specifically between susceptibility to familial early onset psoriasis and human leukocyte antigen (HLA)-Cw6. The basis of this association of the HLA-C locus with disease pathogenesis is, however, not clear, and it is possible that other genes, or a combination of genes, in the HLA region are of functional importance. The MHC S gene is expressed specifically in keratinocyte differentiation and, being located 160 kb telomeric of HLA-C, is a plausible candidate gene. We analysed the allelic distribution of two polymorphisms in the MHC S gene (at +619 and +1243) in a case-control association study. We could confirm a significant association between psoriasis and HLA-Cw6 [odds ratio (OR) = 7.75]. No association was found between disease (or any subtypes) and the MHC S gene polymorphism at position +619, despite its close proximity to HLA-C and the strong linkage disequilibrium between the loci. However, a significant trend with the rarer allele at MHC S (+1243) and psoriasis was detected in the overall data set (OR = 2. 66; P = 2 [times] 10(-)9). This effect was most pronounced in the type 1a (early onset) psoriatics (OR = 3.43). Furthermore, homozygosity for the associated allele at MHC S (+1243) increased the risk of disease over that for carriage of HLA-Cw6 alone (OR = 9. 38), suggesting that allele 2 of MHC S (+1243) provides an additional risk in psoriasis susceptibility. The strong association found here, coupled with the biological involvement of the MHC S gene product corneodesmosin in skin physiology, implicates this locus (or a haplotype across HLA-C and MHC S ) in the impaired desquamation characteristic of psoriasis.

Adult↗
PubMed1999

Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis.

Rheumatoid arthritis (RA) is a common disease of unknown aetiology which usually causes progressive destruction of the joints. Familial aggregation, twin studies and segregation analyses suggest that there is a genetic component to RA and the HLA-DRB1 locus in the major histocompatibility complex on chromosome 6 has been shown to be linked to, and associated with, RA susceptibility. It is likely that other genes with weaker effects are also involved, which may be difficult to detect using conventional parametric and non-parametric linkage methods. We have implemented the combined sib-TDT and TDT, in addition to parametric and non-parametric linkage methods, to investigate the candidate genes of the interleukin-1 (IL-1) gene cluster on chromosome region 2q13, since IL-1 is an important cytokine in the control of the inflammatory response that is central to RA pathology. Several tightly linked IL-1 cluster markers yielded suggestive evidence for linkage in the combined TDT in those families in which affected siblings did not share two HLA-DRB1 alleles identical by descent. The evidence was significant in those with severe disease, as assessed by the presence of bone erosions. In contrast, there was no evidence of linkage using non-parametric linkage analysis, but parametric analysis revealed weak evidence of linkage when marker-trait disequilibrium was incorporated into the analysis. The data provide preliminary evidence for linkage of genes of the IL-1 cluster to RA and suggest a possible role for this region in severe erosive disease.

Arthritis, Rheumatoid↗
PubMed1999

Interleukin-1 genotypes and the association between periodontitis and cardiovascular disease.

An epidemiological association between periodontitis and cardiovascular disease has been reported in multiple studies. Various mechanisms have been proposed as potential explanations for this association, including a common factor that predisposes certain individuals to a hyper-responsive inflammatory response. Variations in the genes that regulate the interleukin-1 (IL-1) response have been associated with both periodontal disease and cardiovascular disease. New data indicate that one pattern of IL-1 genetic polymorphisms, characterized by the IL-1A (+4845) and IL-1B (+3954) markers, is associated with periodontitis but not certain measures of atherosclerosis. Another IL-1 genetic pattern, characterized by the IL-1B (-511) and IL-1RN (+2018) markers, is associated with atherosclerotic plaque formation, as measured by angiography and arterial wall thickness, but not periodontitis. These two patterns also have different functional implications relative to IL-1 biological activity. Studies of IL-1 gene polymorphisms, atherosclerotic plaque instability and cardiovascular clinical events are in progress. Hypothetical models are presented to explain how IL-1 genetic factors may be involved in cardiovascular disease.

Angiography↗
PubMed1999

Possible genetic association between interleukin-1alpha gene polymorphism and the severity of chronic polyarthritis.

Interleukin-1 (IL-1) has been implicated in the pathogenesis of rheumatoid arthritis (RA). IL-1alpha gene polymorphism was analysed for the exon V and promoter region in 51 patients with destructive and 47 with non-destructive RA, as well as in 94 controls. The two biallelic polymorphisms in the promoter region and the exon V were 100% linked. The rare IL-1A2 allele carriage rate was 45% in the control population. It was increased in destructive (54.4%) and decreased in non-destructive RA (26.8%, destructive versus non-destructive, p < 0.007). All indices of disease activity and joint destruction were significantly lower in the patients positive for IL-1A1, and higher in those positive for IL-1A2. The present findings suggest that this IL-1alpha gene polymorphism may contribute to the pathogenesis of chronic polyarthritis. The presence of the IL-1A2 allele could constitute a risk factor for the development of destructive arthritis and could be used early in the course of the disease as a prognostic marker.

Alleles↗
PubMed1998

Interleukin-1 in myocardium and coronary arteries of patients with dilated cardiomyopathy.

Idiopathic dilated cardiomyopathy (DCM) is characterised by a severe dysfunction of the heart muscle resulting in terminal heart failure. Its pathogenesis is believed to be multifactorial involving genetic predisposition, viral infection and autoimmunity, but little is known in detail, and there is no curative treatment except transplantation. Interleukin-1 (IL-1) mediates inflammatory responses to infection and injury. It can be produced by several widely-distributed cell types, including macrophages, and is thought to depress myocyte contractility by stimulating nitric oxide synthase. To investigate whether this pro-inflammatory cytokine may be a pathogenic mediator in DCM, IL-1beta mRNA and protein were evaluated in coronary arteries and myocardium from patients undergoing cardiac transplantation for DCM.IL-1beta mRNA was detected by PCR of cDNA and northern blots of mRNA in coronary arteries and myocardium from patients with DCM. By comparison, samples from patients with ischaemic heart disease (IHD) contained much less IL-1beta mRNA. In contrast, mRNA for other cytokines (TNFalpha, IL-6, IL-10, PDGFA) were similar in both pathologies. In DCM, IL-1beta mRNA and protein were localised to infiltrating macrophages in interstitial regions between myocytes, some of the myocytes themselves, and endothelial cells of vessels in the wall of the arteries. These results suggest that local production of the pro-inflammatory cytokine, IL-1beta may play a part in the pathogenesis of DCM.

Adolescent↗
PubMed1998

An analysis of linkage disequilibrium in the interleukin-1 gene cluster, using a novel grouping method for multiallelic markers.

In population- and family-based association studies, it is useful to have some knowledge of the patterns of linkage disequilibrium that exist between markers in candidate regions. When such studies are carried out with multiallelic markers, it is often convenient to group the alleles into a biallelic system, for analysis. In this study, we specifically examined the interleukin-1 (IL-1) gene cluster on chromosome 2, a region containing candidates for many inflammatory and autoimmune disorders. Data were collected on eight markers, four of which were multiallelic. Using these data, we investigated the effect of three allele-grouping strategies, including a novel method, on the detection of linkage disequilibrium. The novel approach, termed the "delta method," measures the deviation from the expected haplotype frequencies under linkage equilibrium, for each allelic combination. This information is then used to group the alleles, in an attempt to avoid the grouping together of alleles at one locus that are in opposite disequilibrium with the same allele at the second locus. The estimate haplotype frequencies (EH) program was used to estimate haplotype frequencies and the disequilibrium measure. In our data it was found that the delta method compared well with the other two strategies. Using this method, we found that there was a reasonable correlation between disequilibrium and physical distance in the region (r=-.540, P=.001, one-tailed). We also identified a common, eight-locus haplotype of the IL-1 gene cluster.

Alleles↗
PubMed1998

Characterization of a second transcription initiation element (STIE) in the human interleukin-1 beta (IL-1beta) gene.

Interleukin-1-beta (IL-1beta) is a significant mediator in the inflammation process. Although the human IL-1beta genomic sequence has been known for several years, our understanding of its molecular regulation of transcription remains incomplete. We are reporting a new transcription initiation element that is located within intron 1 and exon 2 of the human IL-1beta gene. Different lengths of the human IL-1beta gene fragment (-685 to +550) were cloned upstream from a chloramphenical acetyltransferase (CAT) gene to make the IL-1beta promoter/CAT reporter constructs. Transient CAT expression with these constructs in the human monocytic leukemia cell line THP1 illustrates an important positive regulatory element exists within the region from +387 to +550. Using electromobility shift assays and by DNase I footprinting analysis, we identified three nuclear factor binding sites (+448 to +502, +513 to +531, and +539 to +548). Functional studies show that CAT production is undetectable when the 19 bp region (+513 to +531) is removed, and CAT production is diminished when the 10-bp region (+539 to +548) is deleted. The region containing these sites is likely to initiate a new transcript starting at +559 of exon 2. This second transcript of the IL-1beta gene shares the same reading frame with the previously recognized cDNA transcript.

Base Sequence↗
PubMed1997

Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation.

Tumor necrosis factor alpha (TNF alpha) is a potent immunomodulator and proinflammatory cytokine that has been implicated in the pathogenesis of autoimmune and infectious diseases. For example, plasma levels of TNF alpha are positively correlated with severity and mortality in malaria and leishmaniasis. We have previously described a polymorphism at -308 in the TNF alpha promoter and shown that the rare allele, TNF2, lies on the extended haplotype HLA-A1-B8-DR3-DQ2, which is associated with autoimmunity and high TNF alpha production. Homozygosity for TNF2 carries a sevenfold increased risk of death from cerebral malaria. Here we demonstrate, with reporter genes under the control of the two allelic TNF promoters, that TNF2 is a much stronger transcriptional activator than the common allele (TNF1) in a human B cell line. Footprint analysis using DNase I and B cell nuclear extract showed the generation of a hypersensitive site at -308 and an adjacent area of protection. There was no difference in affinity of the DNA-binding protein(s) between the two alleles. These results show that this polymorphism has direct effects on TNF alpha gene regulation and may be responsible for the association of TNF2 with high TNF alpha phenotype and more severe disease in infections such as malaria and leishmaniasis.

Cell Line↗
PubMed1997

A negative regulatory region containing a glucocorticosteroid response element (nGRE) in the human interleukin-1beta gene.

Interleukin-1 beta (IL-1beta) is one of the most important inflammatory mediators in human inflammatory and immunological diseases. The regulation of human IL-1beta gene expression has been studied for several years, and a few regulatory elements have been discovered in the promoter region. However, little is known about negative regulation of IL-1beta expression at the transcriptional level, which may play an important role in anti-inflammatory and immunosuppressive effects. We have identified a negative regulatory element located in the region between -685 and -395. Within this region, a 19-bp nuclear factor binding site (-570 to -552) was characterized by DNase I footprinting and electromobility shift assay. A consensus sequence for a negative glucocorticoid response element (nGRE) and a transcription activator protein-2 binding site were noted within this footprint. Functional studies showed a 2.5-fold increase in promoter activity when this 19-bp binding site was deleted in the reporter constructs IL-1beta/CAT and IL-1beta/SV40 promoter/CAT. Dexamethasone (10(-8) M) repressed chloramphenicol acetyltransferase (CAT) production by 75% in the wild-type fragment but not in a deletion mutant lacking the 19-bp site. A protein of about 150 kD that bound to this negative regulatory sequence was identified by UV cross-linking. This is the first description of a negative regulatory region responsive to glucocorticoids in a cytokine gene.

Binding Sites↗
PubMed1997

The interleukin-1 genotype as a severity factor in adult periodontal disease.

Although specific bacteria, dental plaque, and age are associated with periodontal disease, there are currently no reliable predictors of periodontitis severity. Studies in twins have suggested a genetic contribution to the pathogenesis of periodontitis, but previous attempts to identify genetic markers have been unsuccessful. The pro-inflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF alpha) are key regulators of the host responses to microbial infection. IL-1 is also a major modulator of extracellular matrix catabolism and bone resorption. We report a specific genotype of the polymorphic IL-1 gene cluster that was associated with severity of periodontitis in non-smokers, and distinguished individuals with severe periodontitis from those with mild disease (odds ratio 18.9 for ages 40-60 years). Functionally, the specific periodontitis-associated IL-1 genotype comprises a variant in the IL-1B gene that is associated with high levels of IL-1 production. In smokers severe disease was not correlated with genotype. In this study, 86.0% of the severe periodontitis patients were accounted for by either smoking or the IL-1 genotype. This study demonstrates that specific genetic markers, that have been associated with increased IL-1 production, are a strong indicator of susceptibility to severe periodontitis in adults.

Adult↗
PubMed1996

TNF2, a polymorphism of the tumour necrosis-alpha gene promoter, is a component of the celiac disease major histocompatibility complex haplotype.

Celiac disease (CD) is an immune disease triggered by the cereal antigen gliadin, resulting in villous atrophy in the small intestine. Susceptibility to the development of CD is strongly influenced by genes in the major histocompatibility complex, in particular alleles of the DQ genes in the class II region. However recent evidence has suggested that the major histocompatibility complex (MHC) class III region may be linked to celiac disease independently of the class II region. Among the genes located in this area is TNF-alpha, which encodes the cytokine tumor necrosis factor-alpha which has a broad range of pro-inflammatory, immunomodulatory and catabolic activities. Therefore, aberrant expression of TNF-alpha could be important in the pathogenesis of MHC-associated immune disorders. A TNF-alpha variant with a polymorphism in its promoter region has been described and designated TNF2. TNF2 has been associated with a variety of MHC-linked diseases, including systemic lupus erythematosus, dermatitis herpetiformis and insulin-dependent diabetes mellitus (IDDM), as well as parasitic infections. TNF2 has previously been shown to be associated with the MHC haplotype HLA A1-B8-DR3-DQ2, which confers susceptibility to CD. We have analyzed the distribution of TNF2 alleles in a group of celiac patients (n = 52) compared to controls (n = 52) in an effort to evaluate its role, if any, in susceptibility to the condition. TNF2 has a frequency of 0.5000 (SE +/- 0.0490) in CD, compared to 0.1635 (+/- 0.0362) in a control sample (p < 10(-6)). Of 52 patients, 44 carried one or more TNF2 alleles. Analysis indicates that the distribution of TNF2 is best explained by assuming 100% allelic association between it and HLA-DQB1*0201 (frequency = 0.7791 +/- 0.0447). However, the number of TNF2 heterozygotes significantly exceeds expectations and measurements of linkage disequilibrium confirm that allelic associations spanning the DQ and TNF regions are strongly maintained in CD. Taken together, these results indicate that TNF2 may have a role in the pathogenesis of CD; however, since it is not an independent association, the possibility that TNF2 constitutes a passive component of the CD haplotype cannot be excluded.

Alleles↗
PubMed1996

Interleukin-1 receptor antagonist allele (IL1RN*2) associated with nephropathy in diabetes mellitus.

We have previously found association between an allele of the interleukin-1 (IL-1) receptor antagonist gene (IL1RN) and several inflammatory diseases, where IL-1 has been implicated in the inflammatory mechanism. We have now, therefore, tested the association of this specific allele (IL1RN*2) with complications of diabetes which have an inflammatory tissue component. We have tested the allele frequency of IL1RN*2 in 128 patients with insulin-dependent and 125 with non-insulin-dependent diabetes mellitus (NIDDM). There was a significant association between carriage of IL1RN*2 and diabetic nephropathy (P<0.001, Pcorrected<0.0012). The association was significant in both types of diabetes, but the observed increase was highest in NIDDM, rising to double the control levels. It appears that IL1RN*2 is a novel genetic marker of severity of inflammatory complications of diseases rather than a marker of disease susceptibility. If the DNA polymorphism is associated with altered gene function, new therapeutic interventions may be possible.

Adult↗