Purchase this article with an account.
Nicole Saksens, Yara Lechanteur, Sanne Verbakel, Joannes Groenewoud, Camiel Boon, Anneke Den Hollander, Carel Hoyng; Association of Family History with Genetic Risk Factors in Patients with Age-Related Macular Degeneration. Invest. Ophthalmol. Vis. Sci. 2013;54(15):6170.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
This study aims to determine the effect of family history on the association of genetic risk factors in patients with age-related macular degeneration (AMD).
A cohort of 486 patients retrieved from the European Genetic Database (EUGENDA) underwent an ophthalmic examination, and were interviewed with a questionnaire about smoking behaviour, body mass index (BMI), and family history. DNA was isolated from venous blood samples and analyzed for 21 single nucleotide polymorphisms (SNPs) known to be associated with AMD. We calculated odds ratios (ORs), adjusted for age, sex, smoking, and BMI with binary logistic regression analysis for the risk allele frequencies in familial AMD patients, using unaffected control individuals as a reference. Furthermore, ORs in familial AMD patients were compared to those in AMD patients without a positive family history (sporadic AMD).
The cohort consists of 93 (19.1%) unrelated AMD patients with a reported positive family history (familial AMD), 230 (47.3%) sporadic AMD patients and 163 (33.5%) control individuals without AMD. Risk alleles in the complement factor H (CFH Y402H) and age-related maculopathy susceptibility 2 (ARMS2 A69S) genes were significantly associated with sporadic and familial AMD as compared to control individuals (CFH OR 1.65 and OR 2.96, respectively. ARMS2 OR 2.71 and OR 2.11, respectively). In patients with familial AMD, the risk allele frequency of CFH Y402H was significantly higher (64.1%) than in the sporadic AMD patients (53.7%, OR 1.55). The risk allele frequency of ARMS2 A69S was not significantly different between familial and sporadic AMD patients. In the familial AMD patients we investigated the number of affected family members. In 10 families at least 4 family members are affected.
Although CFH and ARMS2 risk alleles are associated with both sporadic and familial AMD, the allelic association with the Y402H variant in the CFH gene appears to be stronger in familial AMD. Large, densely affected AMD families are currently being collected to examine the total AMD-associated SNP load and to determine the role of rare highly penetrant variants, using exome sequencing in these families.
This PDF is available to Subscribers Only