Objective. To determine whether functional cytokine gene polymorphisms influence disease susceptibility and phenotype in patients with psoriatic arthritis (PsA).Methods 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 TNF␣ ؊308 and TNF␤ ؉252 polymorphisms (P < 0.0001 and P ‫؍‬ 0.0017, respectively). Frequencies of the TNF␣ ؊308 and TNF␤ ؉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 TNF␤ ؉252 and TNF␣ ؊308 polymorphisms (P ‫؍‬ 0.0003 and P ‫؍‬ 0.0081, respectively). The TNFB2B2 and TNF␣ ؊308 AA genotypes were associated with the earliest mean ages at psoriasis onset.Conclusion. The TNF␣ ؊308 and TNF␤ ؉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.

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The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear.

The IL6 -174 CC genotype may be protective against stroke in those patients who have no history of hypertension. Further studies are required to verify these findings.

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Affected sibling pairs are widely used to identify chromosomal regions harboring genetic loci underlying common disease. We explore the utility of nonparametric sibling pair and family-based association methods to search for disease susceptibility loci in simulated pedigree data for a qualitative disease trait. Logistic regression was used to model genexgene and genexenvironment interactions when significant linkage and association were detected. Using these methods, we were able to detect three of the four susceptibility loci underlying the disease trait with multipoint lod scores of 1.0 or greater. 1999 Wiley-Liss, Inc.

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