Riquelme-Mc Loughlin M Constanza, Granados Julio, Acuña-Alonzo Víctor, Telich-Tarriba José E, Mancilla-Urrea Eduardo, Villa Antonio R, de-Leo Claudia, Alberú Josefina, Morales-Buenrostro Luis E, Madero Magdalena
Escuela de Medicina, Universidad Panamericana.
Rev Invest Clin. 2011 Jul-Aug;63(4):370-5.
Extended major histocompatibility complex (MHC) haplotypes are associated with several autoimmune diseases, and these appear to depend on ancestry.
To evaluate the association of extended MHC gene frequencies, ancestry, and acute rejection.
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).
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 A1B8DR3 was more frequent in donors in whom their recipients had acute rejection (p = 0.008), while A28B39DR4 was more common in the recipients with acute rejection (p = 0.003). Multivariate Cox regression models did not attenuate these associations.
Ancestry and LD may be associated with risk of acute rejection and may therefore be useful in directing immunosuppression.
扩展的主要组织相容性复合体（MHC）单倍型与多种自身免疫性疾病相关，且这些关联似乎取决于祖先血统。
评估扩展的MHC基因频率、祖先血统与急性排斥反应之间的关联。
选取2004年1月至2007年10月在墨西哥城接受肾脏移植且随访至2008年10月的127例活体肾移植受者。主要结局为经活检证实的急性排斥反应。祖先血统被视为美洲印第安人或与高加索人、非洲人或东方人基因的混合血统。估计HLA A、B和DR位点的等位基因和单倍型频率。分析哈迪 - 温伯格（HW）平衡和δ值以检验连锁不平衡（LD）。
各组间基线特征无显著差异。50%为男性，分别有28%、61%和10%的患者共享零个、一个或两个单倍型。所有患者均为西班牙裔且出生于墨西哥。中位群体反应性抗体（PRA）为0%。所有MHC位点的等位基因方差处于HW平衡，14%发生了急性排斥反应。美洲印第安人单倍型频率较高；混合基因和LD在急性排斥反应组中更高。与无急性排斥反应组相比，其受者发生急性排斥反应的供者中，单倍型A1B8DR3更常见（p = 0.008），而在发生急性排斥反应的受者中，A28B39DR4更常见（p = 0.003）。多变量Cox回归模型并未减弱这些关联。
祖先血统和LD可能与急性排斥反应风险相关，因此可能有助于指导免疫抑制治疗。
