Polymorphisms in ARMS2/HTRA1 and complement genes and age-related macular degeneration in India: findings from the INDEYE study.
OBJECTIVE
Association between genetic variants in complement factor H (CFH), factor B (CFB), component 2 (C2), and in the ARMS2/HTRA1 region with age-related macular degeneration (AMD) comes mainly from studies of European ancestry and case-control studies of late-stage disease. We investigated associations of both early and late AMD with these variants in a population-based study of people aged 60 years and older in India.


METHODS
Fundus images were graded using the Wisconsin Age-Related Maculopathy Grading System and participants assigned to one of four mutually exclusive stages based on the worse affected eye (0 = no AMD, 1-3 = early AMD, 4 = late AMD). Multinomial logistic regression was used to derive risk ratios (RR) accounting for sampling method and adjusting for age, sex, and study center.


RESULTS
Of 3569 participants, 53.2% had no signs of amd, 45.6% had features of early amd, and 1.2% had late amd. CFH (RS1061170), C2 (RS547154), OR CFB (RS438999) was not associated with early or late AMD. In the ARMS2 locus, RS10490924 was associated with both early (adjusted RR 1.22, 95% confidence interval [CI]: 1.13-1.33, P < 0.0001) and late AMD (adjusted RR 1.81, 95% CI: 1.15-2.86; P = 0.01); rs2672598 was associated only with early AMD (adjusted RR 1.12, 95% CI: 1.02-1.23; P = 0.02); rs10490923 was not associated with early or late AMD.


CONCLUSIONS
Two variants in ARMS2/HTRA1 were associated with increased risk of early AMD, and for one of these, the increased risk was also evident for late AMD. The study provides new insights into the role of these variants in early stages of AMD in India.
Department of Genetics, Dr G Venkataswamy Eye Research Institute, Aravind Medical Research Foundation, Aravind Eye Hospital, Madurai, Tamil Nadu, India.
Periasamy
P
Sundaresan
Praveen
P
Vashist
Ravilla D
RD
Ravindran
Ashwini
A
Shanker
Dorothea
D
Nitsch
Bareng A S
BA
Nonyane
Liam
L
Smeeth
Usha
U
Chakravarthy
Astrid E
AE
Fletcher
D000368:Aged; D003175:Complement C2 / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D007194:India / Q000453:epidemiology; D008268:Macular Degeneration / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012697:Serine Endopeptidases / Q000235:genetics* / Q000378:metabolism
C514392:ARMS2 protein, human; D003175:Complement C2; D011506:Proteins; D004247:DNA; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases