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A Polymorphism at Position +874 in The IFN-γ Gene is Associated with Susceptibility for Dilated Cardiomyopathy

Erika Lindberg, Bert Andersson, Robert Eggertsen, Ernst Nyström and Yvonne Magnusson

The etiology of idiopathic dilated cardiomyopathy (DCM) is largely unknown. One hypothesis is that immunological factors are responsible for disease development. Single nucleotide polymorphisms (SNP) at position +874 of the IFN-γ gene and at position -168 of the MHC2TA gene have previously been shown to associate with infl ammatory and autoimmune disorders. We analysed their possible infl uence on susceptibility and prognosis in patients with DCM. Genotypes were determined by real-time PCR in 442 patients and 425 controls. Genotype frequencies were found signifi cantly different between patients and controls for IFN-γ (p=0.029), but not for MHC2TA (p=0.26). In a logistic regression analysis, the high producing TT genotype of IFN-γ was signfi cantly more common in patients than controls (OR 1.55 [1.12-2.15], p=0.009). None of the polymorphisms had an infl uence on long-term outcome, 10-years mortality with a HR of 0.94 (p=0.74) and 0.85 (p=0.30), IFN-γ and MHC2TA, respectively. A 50% higher risk to develop DCM for individuals with the TT genotype of the IFN- gene is a new finding and emphasize the role of IFN- in DCM pathology.