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Susan M. Nicholls, Louisa K. Mitchard, Ricardo Pong-Wong, Ross Harley, Andrew D. Dick, Alan L. Archibald, Michael Bailey; Corneal Transplant Rejection In NIH Miniature Swine Is Associated With Donor-recipient Mismatches In A Region Containing The Homologue Of The Mouse Zfp106 Gene Encoding The H3a Antigen. Invest. Ophthalmol. Vis. Sci. 2012;53(14):6899.
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© ARVO (1962-2015); The Authors (2016-present)
To identify DNA polymorphisms associated with corneal graft rejection in a semi-inbred pig model.
Corneal transplants were performed using three MHC homozygous lines of pig and monitored for rejection. DNA was isolated from blood obtained from allograft donors and recipients at transplantation. DNA samples were genotyped for single nucleotide polymorphisms (SNPs) using the Illumina PorcineSNP60 chip (59,852 SNPs analysed). Genetic disparities associated with rejection were identified by logistic regression using log likelihood ratios. A 5% significance threshold was calculated by permutation to correct for multiple tests.
Of sixteen transplants performed across full (major histocompatibility complex [MHC] and minor) mismatches, ten transplants were rejected within 90 days. Five intrastrain transplants, performed across minor mismatches only, were not rejected. Consistent with studies indicating that MHC antigens are not important targets for rejection, none of the SNPs significantly associated with rejection were located on chromosome 7, which contains the pig MHC. However, regions containing SNPs significantly associated with rejection were found on chromosome 1 between 125 and 138 Mb (Sscrofa9) and on chromosome 6 between 7.7 and 7.8 Mb (Sscrofa9). Interestingly, the region on Chromosome 1, in which ca. 160 protein coding genes have been annotated, contains the pig homologue of the H3a gene (Zfp106), previously shown to be associated with corneal graft rejection in mice. The porcine beta-2-microglobulin (B2M) gene also maps to the region of interest on chromosome 1.
The finding that the same locus may be involved in rejection of corneal grafts in two mammalian species, pig and mouse, strongly suggests that it may also be an important determinant of human corneal transplant rejection. Lack of rejection of MHC-matched transplants is likely to have been due to a high level of intrastrain genomic homozygosity.
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