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Study of polymorphisms in CFH, ARMS2 and HTRA1 genes as potential risk factors for age related macular degeneration in Indian patients

Divya Gupta, Vani Gupta, Vinita Singh, Shobhit Chawla, Prajnya Ranganath, Shubha R. Phadke*


Background: Age-related macular degeneration (AMD) is a common disease in which both environmental and genetic factors have been implicated. Various single nucleotide polymorphisms (SNPs) have been found to be associated with AMD.

Aim: To study the association of polymorphisms in CFH, ARMS2 and HTRA1 genes with AMD in Indian patients.

Settings and Design: Case-control study

Methods and Material: Genotyping for CFH (Y402H), ARMS2 (A69S), HTRA1 (promoter region G/A) were performed in 121 AMD patients and 100 controls by PCR-RFLP.

Statistical Analysis Used: Hardy-Weinberg estimates (HWE) were calculated. Analysis for genotypes was done under additive, recessive as well as dominant models of inheritance showing odds of occurrence using Fisher’s exact test. Pairwise linkage disequilibrium (LD) was measured using SNPStats to predict Lewontin’s LD (D’) and correlation coefficient (r).

Results: Genotype analysis of all three polymorphisms (Y402H in CFH, A69S in ARMS2 and G/A in HTRA1 promoter region) showed the strongest association of AMD with Y402H polymorphism in CFH gene. Odds ratio for Y402H allele in CFH gene was 2.66 under recessive model. Odds ratio for polymorphisms in ARMS2 and HTRA1 genes were 2.41 and 1.97 respectively. Significant LD (D’=0.87, r=0.81) was observed in the presence of variant alleles HTRA1A and ARMS2T for AMD.

Conclusions: Present study suggests that all the three polymorphisms CFH Y402H (T/C), ARMS2 A69S (G/T) and HTRA1 promoter region (G/A) alleles are potential risk factors and are independently associated with AMD in Indian population. Detection of individuals at risk could lead to strategies for prevention, early diagnosis and management of AMD.


AMD; ARMS2; CFH; HTRA1; Indian; Polymorphism; PCR-RFLP

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