title: LOC387715/HTRA1 polymorphisms, smoking and combined effects on exudative age-related macular degeneration in a Korean population.
abstract: BACKGROUND
  This study was to investigate the association of two single nucleotide polymorphisms (SNPs) in LOC387715 and HTRA1 with exudative age-related macular degeneration (AMD) in a Korean population and the gene-gene and gene-environment interactions in the development of AMD.
  
  
  METHODS
  We genotyped two SNPs that are located in the LOC387715 locus (rs10490924) and HTRA1 (rs11200638) in 137 cases of exudative AMD and 187 controls.
  
  
  RESULTS
  Both two SNPs were significantly associated with AMD (P = 0.0001). Homozygotes for the risk allele at LOC387715 and HTRA1 had a 3.80-fold and a 4.03-fold increased risk of exudative AMD, respectively, compared with homozygotes for the wild-type allele (P = 0.0001). The joint effects for complement factor H (CFH) Y402H and 10q26 variants indicated an increased risk of exudative AMD. The odds ratios (ORs) of AMD for individuals carrying one-, two- and three-copy risk alleles of CFH Y402H and LOC387715 were 1.08, 3.49 and 3.64, respectively. Also, the combination effect of the CFH Y402H risk alleles with HTRA1 risk alleles was dose-dependent. The interaction analysis between gene and environmental factors showed that among several factors, smoking synergistically increased the susceptibility of AMD for variants of LOC387715 and HTRA1, with OR 8.33 (3.05-22.74) and OR 8.50 (3.07-23.51), respectively.
  
  
  CONCLUSIONS
  This study demonstrated the significant association of the 10q26 SNPs (HTRA1 and LOC387715) in an AMD cohort from Korea and was consistent with previous studies from other populations. Also, a statistically significant interaction between genetic and environmental factors was found.
authors.affiliation: Department of Ophthalmology, Inha University School of Medicine, Incheon, Korea.
authors.forename: Soo J
authors.initials: SJ
authors.lastname: Lee
authors.forename: Na R
authors.initials: NR
authors.lastname: Kim
authors.forename: Hee S
authors.initials: HS
authors.lastname: Chin
mesh_terms: D000368:Aged; D000483:Alleles; D044466:Asian People; D015331:Cohort Studies; D017242:Complement Factor H / Q000235:genetics; D005122:Exudates and Transudates / Q000378:metabolism*; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006720:Homozygote; D006801:Humans; D008268:Macular Degeneration / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D012697:Serine Endopeptidases / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; D011506:Proteins; D017242:Complement Factor H; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases