Extended major histocompatibility complex haplotypes, ancestry and acute kidney transplant rejection in Mexicans.

INTRODUCTION: Extended major histocompatibility complex (MHC) haplotypes are associated with several autoimmune diseases, and these appear to depend on ancestry. OBJECTIVE: To evaluate the association of extended MHC gene frequencies, ancestry, and acute rejection. MATERIAL AND METHODS: 127 living kidney transplant recipients who underwent kidney transplantation in Mexico City between January 2004 and October 2007 with follow up until October 2008. The primary outcome was biopsy proven acute rejection. Ancestry was considered as either Amerindian or admixtures with Caucasian, African or Oriental genes. Allele and haplotype frequencies were estimated for HLA A, B and DR loci. Hardy Weinberg (HW) and delta values were analyzed to test for linkage disequilibrium (LD). RESULTS: There were no significant differences in the baseline characteristics between groups. 50% were men, and 28, 61 and 10% of the patients shared zero, one or two haplotypes, respectively. The whole population was Hispanic and born in Mexico. Median PRA was 0%. Allelic variance in all MCH loci was in HW equilibrium, 14% developed acute rejection. There was a high frequency of Amerindian haplotypes; admixture genes and LD were higher in the group with acute rejection. When compared to the group without acute rejection, the haplotype A1*B8*DR3 was more frequent in donors in whom their recipients had acute rejection (p = 0.008), while A28*B39*DR4 was more common in the recipients with acute rejection (p = 0.003). Multivariate Cox regression models did not attenuate these associations. CONCLUSIONS: Ancestry and LD may be associated with risk of acute rejection and may therefore be useful in directing immunosuppression.