title: Association of the del443ins54 at the ARMS2 locus in Indian and Australian cohorts with age-related macular degeneration.
abstract: OBJECTIVE
  The ARMS2/HTRA1 genes at the 10q26 locus have been associated with risk of age-related macular degeneration (AMD), with the most significantly associated variants being A69S (rs10490924), del443ins54 (EU427539) and rs11200638. We wished to explore the association of the del443ins54 in two ethnically different populations from India and Australia.
  
  
  METHODS
  The del443ins54 was screened in a large cohort of ~1500 subjects from these two populations by a combination of PCR-based agarose gel electrophoresis and validated by resequencing. Statistical analysis comprised the calculations of allele, genotype and haplotype frequencies along with their p values and corresponding odds ratios (OR), and 95% confidence intervals (95% CI) and measures of linkage disequilibrium (LD).
  
  
  RESULTS
  The del443ins54 was significantly associated with AMD in both the Indian (p=1.74 × 10(-13); OR = 2.80, 95%CI, 2.12-3.70) and Australian cohorts (p = 2.78 × 10(-30); OR = 3.15, 95%CI, 2.58-3.86). These associations were similar to those previously identified for the A69S and the rs11200638 variant in these populations that also exhibited high degrees of LD (D' of 0.87-0.99). A major risk haplotype of "T-indel-A" (p = 5.7 × 10(-16); OR = 3.16, 95%CI, 2.34-4.19 and p=6.33 × 10(-30); OR = 3.15, 95%CI, 2.57-3.85) and a protective haplotype of "G-wild type-G" (p=2.35 × 10(-11); OR = 0.39, 95%CI, 0.29-0.52 and p=1.02 × 10(-30); OR = 0.31, 95%CI, 0.25-0.38) were identified in the Indian and Australian cohorts, respectively.
  
  
  CONCLUSIONS
  These data provide an independent replication of the association of del443ins54 variant in two different ethnicities, despite differences in allele and haplotype frequencies between them. High levels of LD in both populations limit further genetic dissection of this region in AMD.
authors.affiliation: Hyderabad Eye Research Foundation, LV Prasad Eye Institute, Hyderabad, India.
authors.forename: Inderjeet
authors.initials: I
authors.lastname: Kaur
authors.forename: Stuart
authors.initials: S
authors.lastname: Cantsilieris
authors.forename: Saritha
authors.initials: S
authors.lastname: Katta
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Richardson
authors.forename: Maria
authors.initials: M
authors.lastname: Schache
authors.forename: Rajeev R
authors.initials: RR
authors.lastname: Pappuru
authors.forename: Raja
authors.initials: R
authors.lastname: Narayanan
authors.forename: Annie
authors.initials: A
authors.lastname: Mathai
authors.forename: Ajit B
authors.initials: AB
authors.lastname: Majji
authors.forename: Nicole
authors.initials: N
authors.lastname: Tindill
authors.forename: Robyn H
authors.initials: RH
authors.lastname: Guymer
authors.forename: Subhabrata
authors.initials: S
authors.lastname: Chakrabarti
authors.forename: Paul N
authors.initials: PN
authors.lastname: Baird
mesh_terms: D001315:Australia; D015331:Cohort Studies; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D056426:Genetic Loci / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007194:India; D015810:Linkage Disequilibrium / Q000235:genetics; D008268:Macular Degeneration / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D012307:Risk Factors; D012697:Serine Endopeptidases / Q000235:genetics
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases