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Secondly, HIV infects the lymphocytes and macrophages that enter the kidney, resulting in the release of inflammatory lymphokines or cytokines which promote injury and fibrosis[27]. In addition, there are studies that have demonstrated that CCR5 and CXCR4, the two main HIV co-receptors, that mediate entry of HIV strains into susceptible cells, are not expressed by intrinsic renal cells, but are expressed in circulating and infiltrating leukocytes at sites of tubulo-interstitial inflammation[28]. GENETIC PREDISPOSITION TO CHRONIC KIDNEY DISEASE IN PATIENTS OF AFRICAN ANCESTRY Genetic variation plays an important role in susceptibility http://www.selleckchem.com/products/E7080.html to common forms of disease such as diabetes, hypertension and kidney disease, with marked differences in the prevalence and sometimes the presentation, according to ethnicity and ancestry. African Americans have four times the incidence of ESRD when compared to Americans of European ancestry, supporting a causal role for genetics in the aetiology of kidney disease[12,13,29]. These observations led to the use of ancestry informative population variation data to help explain this disparity. In 2008, two find protocol groups published papers back to back in Nature Genetics, heralding the discovery of genetic association of markers in the non-muscle myosin heavy chain 9 (MYH9) gene on chromosome 22 with non-diabetic ESRD[30] and FSGS[31] in African Americans (Figure ?(Figure11 and Table ?Table2).2). Both PIK-3 groups used genome wide admixture mapping approaches in their analysis, showing that increased African ancestry was correlated with increased susceptibility. Figure 1 Historical timeline reflecting the discovery of genetic association to chronic kidney disease in populations with African ancestry. 1Adapted from Kopp et al[31] and Kao et al[30]; 2Adapted from Freedman et al[49], Genovese et al[13], Tzur et al[29]; ... Table 2 Summary of the studies of MYH9 and APOL1 variants The transatlantic slave trade in the 16th to 19th centuries brought in an estimated 12 million individuals from Africa (mainly West Africa) to enslavement in America[32,33] and this was the driver for the introduction of African genetic variation to America. As a consequence of this population relocation, admixture occurred with Native Americans (Amerindians) and Europeans leading to mixed genomic profiles among the group now referred to as African Americans. African Americans have, on average, about 80% African ancestry, although there are regional differences across the country[34].