Sequence variants in HTRA1 and LOC387715/ARMS2 and phenotype and response to photodynamic therapy in neovascular age-related macular degeneration in populations from Israel
2008

Genetic Variants Linked to Age-Related Macular Degeneration in Israeli Populations

Sample size: 255 publication Evidence: high

Author Information

Author(s): Itay Chowers, Meir Tal, Michal Lederman, Nitza Goldenberg-Cohen, Yoram Cohen, Eyal Banin, Edward Averbukh, Itzhak Hemo, Ayala Pollack, Ruth Axer-Siegel, Orly Weinstein, Josephine Hoh, Donald J. Zack, Tural Galbinur

Primary Institution: Hadassah-Hebrew University Medical Center, Jerusalem, Israel

Hypothesis

Are SNPs in LOC387715/ARMS2 and HTRA1 associated with age-related macular degeneration and its response to therapy in Israeli populations?

Conclusion

The rs10490924 SNP in LOC387715/ARMS2 and the rs11200638 SNP in HTRA1 are strongly associated with neovascular age-related macular degeneration in this Israeli population.

Supporting Evidence

  • Both SNPs were in almost complete linkage disequilibrium.
  • Homozygotes for the T allele of rs10490924 had an odds ratio of 8.6 for having AMD.
  • Homozygotes for the A allele of rs11200638 had an odds ratio of 10.7 for having AMD.
  • Genotyping was performed on 255 NVAMD patients and 119 unaffected controls.
  • HTRA1 mRNA levels were not associated with rs11200638 genotypes.
  • Significant associations were found among Ashkenazi Jews, Sephardic Jews, and Arabs.
  • Smoking was associated with an increased risk for AMD.
  • HTRA1 expression levels were similar in different genotypes.

Takeaway

This study found that certain genetic changes are linked to a common eye disease in people from Israel, but they don't seem to affect how well patients respond to treatment.

Methodology

Genotyping for specific SNPs was performed on 255 NVAMD patients and 119 unaffected controls, with correlations made to phenotype and therapy response.

Limitations

The study did not find significant associations between SNPs and various clinical characteristics or response to therapy.

Participant Demographics

Participants included Ashkenazi Jews, Sephardic Jews, and Arabs, with a balanced gender ratio.

Statistical Information

P-Value

p<0.00001

Confidence Interval

95% CI of 3.5–20.8 for rs10490924 and 95% CI of 3.2–35.7 for rs11200638

Statistical Significance

p<0.00001

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