Ethnicity and cytokine gene polymorphism

Ethnicity clearly is associated with dramatic differences in cytokine polymorphism distributions. The disparity between graft survival rates among African-American and other populations suggests that the cytokine polymorphisms described by many laboratories, including our own (Lo et al., 2004; Egidi and Gaber, 2003; Hartwig et al., 1993; Hardinger et al., 2001; Lo et al., 2001; Ilyas et al., 1998), may play an incremental role in ethnic-based survival rates and subsequent differences in immune reactivity. Indeed, there is a documented deficit in long-term allograft survival for African-Americans as compared to Caucasian, Hispanic, and Asian populations (USRDS, 2000). Poor graft survival among African-Americans had been attributed in part to socioeconomic factors and to inferior HLA matching. African-American donor kidneys also have been associated with a worse graft survival (Yates et al., 2003). Studies examining potential effects of polymorphisms on pharmacokinetics and immune responsiveness have also been performed showing that peripheral blood cells from healthy adult

African-Americans express significantly more B7 costimulatory molecules (CD80, CD86) than Caucasians and mount more vigorous immune responses to mitogens and antigens in vitro (Hutchings et al., 1999; Lindholm et al., 1992; Tornatore et al., 1995). Factors such as these could represent additional key factors for racial variation in allograft loss (Cox et al., 2001; Kerman et al., 1991; Gaston et al., 1992). There are striking differences in the distribution of cytokine polymorphisms among ethnic populations (Hoffmann et al., 2002; Cox et al., 2001). Blacks, Hispanics and Asians have marked differences in their inheritance of IL-6 alleles and IL-10 genotypes that result in high expression when compared with Caucasian. High IL-6 producing individuals have previously been shown to be at heightened risk for ACR and/or some forms of end-stage renal disease (Casiraghi et al., 1997; Hoffmann et al., 2003). The high production of IL-6 in concert with pro-inflammatory cytokines, may result in an increase risk for allograft rejection in the African-American population, or at least increase the impact of alterations in immunosuppressive non-compliance. While, Asians exhibit IFN-gamma genotypes that result in diminished cytotoxic effects thereby a decrease risk of acute graft rejections. This observation suggests that a population of recipients more prone to ACR may be predicted through study of cytokine gene polymorphisms.

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