title: A cross-ethnicity investigation of genes previously implicated in primary angle closure glaucoma.
abstract: OBJECTIVE
  To investigate the underlying genetic variation between candidate genes and primary angle closure glaucoma (PACG) in both Nepalese and Australian populations.
  
  
  METHODS
  A total of 213 patients with PACG (106 Nepalese and 107 Australian) and 492 age and sex matched controls (204 Nepalese and 288 Australian) were included in the current study. Three candidate genes were selected; methyl-tetrahydrofolate reductase (MTHFR), calcitonin receptor-like receptor gene (CALCRL), and membrane frizzled-related protein (MFRP). Tag single nucleotide polymorphisms (SNPs) were selected and genotyped to capture the majority of common variation across each locus. Allele and haplotype analyses were conducted using PLINK.
  
  
  RESULTS
  SNPs in the nanophthalmos gene MFRP were found to be nominally associated with PACG under the allelic model. Two SNPs were associated in the Australian cohort (rs948414; p=0.02 and rs36015759; p=0.02), and a single SNP in the Nepalese cohort (rs10790289; p=0.03), however these SNPs failed to remain significant after adjustment for sex and age. A haplotype at the CALCRL gene (AATACAGAT) was associated in the Australian cohort (corrected p-value=0.024). No association was observed in either cohort for MTHFR.
  
  
  CONCLUSIONS
  This study implicates genetic variation at the CALCRL gene in the pathogenesis of PACG in an Australian Caucasian cohort. Additionally, the MFRP gene shows tendency to be associated with PACG in both the Australian and Nepalese cohorts. Further investigation in a larger cohort is warranted to confirm these findings. No statistically significant associations were identified between MTHFR and PACG in either population.
authors.affiliation: Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. awad0002@flinders.edu.au
authors.forename: Mona S
authors.initials: MS
authors.lastname: Awadalla
authors.forename: Kathryn P
authors.initials: KP
authors.lastname: Burdon
authors.forename: Suman S
authors.initials: SS
authors.lastname: Thapa
authors.forename: Alex W
authors.initials: AW
authors.lastname: Hewitt
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Craig
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D044466:Asian People; D001315:Australia / Q000453:epidemiology; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics*; D016022:Case-Control Studies; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D015812:Glaucoma, Angle-Closure / Q000208:ethnology* / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009390:Nepal / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D044465:White People; D000099274:Frizzled-Related Proteins
chemical_list: D058286:Calcitonin Receptor-Like Protein; D008565:Membrane Proteins; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C545578:CALCRL protein, human; C490110:MFRP protein, human; D000099274:Frizzled-Related Proteins; C573423:MTHFR protein, human