[Genetic factors associated with age-related macular degeneration].
Age related macular degeneration (AMD) is the leading cause of vision loss in the elderly in developed countries. Genetic factors play a major role in this multifactorial and polygenic disease. Genomewide analysis identified two loci on 1q25-31 and 10q26 chromosomes associated with AMD, and association studies highlighted the implication of SNPs located in the complement H factor gene (CFH) on 1q25-31 and in PLEKHA1-HTRA1-LOC387715 on 10q26 in the disease. Homozygous carriers for the at-risk alleles of the CFH, HTRA1, and LOC387715 genes have an increased risk to develop exudative AMD with odds ratio of 6.2, 6.9, et 7.3 respectively. Moreover, other genes involved in the complement cascade, namely the genes of the C2, C3 component, and factor B, are associated to the disease. The SCARB1 gene has also recently been associated to AMD. Genotype-phenotype correlations have been performed in AMD patients and found that occult CNV are more often associated to CFH at-risk allele and classic CNV to HTRA1 at-risk allele. This last allele seems also linked to more severe forms of the disease. These new major genetic factors could lead to a new clinical approach of AMD and to the discovery of new therapeutic targets.
Leveziel
Nicolas
N
hôpital intercommunal de Créteil, avenue de Verdun, Créteil, France. nicolas.leveziel@yahoo.fr
Puche
Nathalie
N
Zerbib
Jennyfer
J
Benlian
Pascale
P
Coscas
Gabriel
G
Soubrane
Gisèle
G
Souied
Eric
E
D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000502:physiology; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D053327:Apolipoprotein E4 / Q000235:genetics / Q000502:physiology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002986:Clinical Trials as Topic; D017242:Complement Factor H / Q000235:genetics / Q000502:physiology; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000502:physiology; D008268:Macular Degeneration / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D009765:Obesity / Q000453:epidemiology; D010641:Phenotype; D011506:Proteins / Q000235:genetics / Q000502:physiology; D012697:Serine Endopeptidases / Q000235:genetics / Q000502:physiology; D012907:Smoking / Q000009:adverse effects
C056475:ABCA4 protein, human; C514392:ARMS2 protein, human; D018528:ATP-Binding Cassette Transporters; D020533:Angiogenesis Inhibitors; D053327:Apolipoprotein E4; C493495:CFH protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C435927:PLEKHA1 protein, human; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases