1. Complement Factor H Polymorphism in Age- Related Macular Degeneration* *Klein RJ, et al. Science. 2005; 308: 385-89.

2. Overview Introduction Methods Results Discussion 2

3. Age-Related Macular Degeneration (AMD) Leading cause of blindness in elderly Gradual destruction of central field vision Key feature is drusen Risk factors 3

4. http://www.allaboutvision.com/conditions/amd.htm 4

5. Methods Whole-genome case-control association study Subset of Age-Related Eye Disease Study N=146: 96 cases, 50 controls All were genotyped Bonferroni correction 5

6. Allelic Associations 103, 611 SNPS analyzed 2 SNPS, rs380390 & rs10272438, significant rs10272438 out of Hardy-Weinberg equilibrium & no longer significant Selection of another SNP: rs1329428 6

7. Figure 1 7

8. Table 1 Attributers380390 (C/G)rs1329428 (C/T) Risk alleleCC Allelic association χ 2 nominal P value4.1 × 10 −8 1.4 × 10 −6 Odds ratio (dominant) (95% CI)4.6 (2.0–11)4.7 (1.0–22) PAR (95% CI)70% (42–84%)80% (0–96%) Frequency in HapMap CEU0.700.82 Odds ratio (recessive) (95% CI)7.4 (2.9–19)6.2 (2.9–13) PAR (95% CI)46% (31–57%)61% (43–73%) Frequency in HapMap CEU0.230.41 8

9. Figure 2 9

10. Candidate markers Identified N1 haplotype with highest risk Re-sequenced exons of 96 participants Found SNP in exon 9 of CFH w/ tyrosine- histidine change 10

11. 11 Discussion Linkage scans associate CFH w/ AMD C5b-9 complex found in drusen Immunofluorescence confirms CFH in eyes w/ AMD

12. 12 Conclusion Age & smoking affect plasma levels of CFH Histidine variant almost always occurs in AMD Additional studies to examine tyrosine- histidine role in AMD

13. References Facts about age-related macular degeneration, NEI, National Institute of Health, http://www.nei.nih.gov/health/macularde gen/armd_facts.asp. Podgor MJ, Leske MC, Ederer F. Incidence estimates for lens changes, macular changes, open-angle glaucoma and diabetic retinopathy. Am J Epidemiol. 1983;118:208-212. 13

14. Figure 3 14