MyVisionTest News Archive
Oct 14, 2009
Complement factor H genotype increases risk of bilateral AMD
Persons with the CFH CC genotype have an increased likelihood of bilateral compared with unilateral age-related macular degeneration (AMD), according to a new study.
AMD is an irreversible debilitating disease with complex genetic and environmental contributors. Recent research has focused on identifying the genetic predisposition to AMD, and complement factor H (CFH), LOC387715, and HTRA1 are the principal documented gene loci responsible. A meta-analysis has indicated that CFH CC and CT genotypes are responsible for 58.9% of AMD cases, implying that more than half of AMD cases may be attributable to the CFH Y402H polymorphism.
Research studies have suggested that diseases involving bilateral organs have an underlying genetic predisposition. Bilateral breast cancer and testicular germ cell tumors are 2 examples. Whether the CFH CC or CT genotypes increase the likelihood or age at onset of bilateral involvement by AMD lesions is unclear, with only limited data from the literature addressing this association.
Methods and Results
The Blue Mountains Eye Study (BMES) followed up 3654 participants 49 years and older (BMES 1, 1992-1994), including 2335 (75.3% of survivors) at the 5-year (BMES 2, 1997-1999) and 1952 (76.5%) at the 10-year (BMES 3, 2002-2004) examinations. Age-related macular degeneration retinal photographic grading used the Wisconsin system. Early and late AMD included prevalent and incident cases from all visits. CFH genotyping used TaqMan assays.
Of 767 AMD cases, 53.3% of early and 53.1% of late AMD cases were bilateral. After adjusting for age and other covariants, the CFH CC (Y402H polymorphism) genotype was associated with an increased likelihood of bilateral compared with unilateral involvement by any soft drusen (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.4-4.5), distinct soft drusen (OR, 2.8; 95% CI, 1.0-8.1), and pigmentary abnormalities (OR, 1.7; 95% CI, 1.0-2.8). We could not establish significant associations between this genotype and the bilaterality of late AMD (OR, 1.8; 95% CI, 0.4-7.7), either geographic atrophy (OR, 0.6; 95% CI, 0.07-4.6) or neovascular AMD (OR, 3.4; 95% CI, 0.3-41.4).
Discussion and Conclusions
Bilateral involvement is typical in AMD, increasing in frequency with age. Bilateral AMD, especially the advanced stage of AMD, commonly results in legal blindness and, thus, carries greater clinical significance than unilateral disease.
Similar to other diseases affecting bilateral organs, genetic predisposition may play a role. The CFH gene and its relevant complement cascade are now confirmed to be strongly associated with AMD.
This study found that the homozygous CFH CC genotype is significantly associated with bilateral AMD (any early or late) and bilateral distinct soft drusen. Soft drusen have been shown to signify a high risk of progression to late AMD.
In conclusion, this study has shown that the CFH Y402H homozygous CC genotype is significantly associated with bilateral compared with unilateral presence of any AMD or of soft drusen, independent of age, sex, smoking, and WBC count. These findings suggest a genetic predisposition for an earlier development of bilateral involvement by some early AMD lesions.
Read more...
Arch Ophthalmol. 2009 Oct;127(10):1339-44
Tags: AMD, genetics, complement
Persons with the CFH CC genotype have an increased likelihood of bilateral compared with unilateral age-related macular degeneration (AMD), according to a new study.AMD is an irreversible debilitating disease with complex genetic and environmental contributors. Recent research has focused on identifying the genetic predisposition to AMD, and complement factor H (CFH), LOC387715, and HTRA1 are the principal documented gene loci responsible. A meta-analysis has indicated that CFH CC and CT genotypes are responsible for 58.9% of AMD cases, implying that more than half of AMD cases may be attributable to the CFH Y402H polymorphism.
Methods and Results
The Blue Mountains Eye Study (BMES) followed up 3654 participants 49 years and older (BMES 1, 1992-1994), including 2335 (75.3% of survivors) at the 5-year (BMES 2, 1997-1999) and 1952 (76.5%) at the 10-year (BMES 3, 2002-2004) examinations. Age-related macular degeneration retinal photographic grading used the Wisconsin system. Early and late AMD included prevalent and incident cases from all visits. CFH genotyping used TaqMan assays.
Of 767 AMD cases, 53.3% of early and 53.1% of late AMD cases were bilateral. After adjusting for age and other covariants, the CFH CC (Y402H polymorphism) genotype was associated with an increased likelihood of bilateral compared with unilateral involvement by any soft drusen (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.4-4.5), distinct soft drusen (OR, 2.8; 95% CI, 1.0-8.1), and pigmentary abnormalities (OR, 1.7; 95% CI, 1.0-2.8). We could not establish significant associations between this genotype and the bilaterality of late AMD (OR, 1.8; 95% CI, 0.4-7.7), either geographic atrophy (OR, 0.6; 95% CI, 0.07-4.6) or neovascular AMD (OR, 3.4; 95% CI, 0.3-41.4).
Discussion and Conclusions
Bilateral involvement is typical in AMD, increasing in frequency with age. Bilateral AMD, especially the advanced stage of AMD, commonly results in legal blindness and, thus, carries greater clinical significance than unilateral disease.
Similar to other diseases affecting bilateral organs, genetic predisposition may play a role. The CFH gene and its relevant complement cascade are now confirmed to be strongly associated with AMD.
This study found that the homozygous CFH CC genotype is significantly associated with bilateral AMD (any early or late) and bilateral distinct soft drusen. Soft drusen have been shown to signify a high risk of progression to late AMD.
In conclusion, this study has shown that the CFH Y402H homozygous CC genotype is significantly associated with bilateral compared with unilateral presence of any AMD or of soft drusen, independent of age, sex, smoking, and WBC count. These findings suggest a genetic predisposition for an earlier development of bilateral involvement by some early AMD lesions.
Read more...
Arch Ophthalmol. 2009 Oct;127(10):1339-44
