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S. V. Goverdhan, J. R. Heckenlively, M. Othman, K. H. Branham, H. Griffiths, A. Swaroop, A. J. Lotery; HLA Genotypes and Age Related Macular Degeneration: A Replication Study in a North American Cohort. Invest. Ophthalmol. Vis. Sci. 2007;48(13):3008.
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© ARVO (1962-2015); The Authors (2016-present)
To test and validate the previously reported novel HLA-AMD associations (Cw*0701, B*4001 and DRB1*1301) in a North American cohort of AMD cases and controls.
DNA samples were obtained from a cohort of 576 AMD cases and 288 controls from Michigan, USA. Genotyping for HLA alleles was done using methods described previously. Frequencies for the tested alleles in the Michigan AMD group (n=576) were then compared with those in their normal controls (n=288). P values were obtained by Fisher’s exact tests with bonferroni correction.
Data analysis demonstrated a trend similar to the UK cohort. The positive AMD association with class I Cw*0701 (P=0.017), the negative AMD associations with HLA class I allele B*4001 (P=0.046) and class II allele DRB1*1301 (P=0.009) were found to be significant. After correcting for multiple comparisons, the previous positive association of Cw*0701 just missed significance (Pc=0.05) and the negative association of DRB1*1301 (Pc=0.02) remained significant while the B*4001 (Pc=0.13) did not reach significance. The lower HLA-Cw*0701 frequencies seen in the Michigan normal controls as compared to the UK controls seem to mirror the reported population differences in allelic distributions (US vs. Western Europe, 0.14 and 0.21 respectively).
HLA associations could play an important role in AMD pathogenesis. Larger HLA-AMD studies in different ethnic populations are further needed to confirm these novel HLA-AMD associations.
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