Association of high myopia with crystallin beta A4 (CRYBA4) gene polymorphisms in the linkage-identified MYP6 locus.
PLoS One
; 7(6): e40238, 2012.
Article
em En
| MEDLINE
| ID: mdl-22792142
ABSTRACT
BACKGROUND:
Myopia is the most common ocular disorder worldwide and imposes tremendous burden on the society. It is a complex disease. The MYP6 locus at 22 q12 is of particular interest because many studies have detected linkage signals at this interval. The MYP6 locus is likely to contain susceptibility gene(s) for myopia, but none has yet been identified. METHODOLOGY/PRINCIPALFINDINGS:
Two independent subject groups of southern Chinese in Hong Kong participated in the study an initial study using a discovery sample set of 342 cases and 342 controls, and a follow-up study using a replication sample set of 316 cases and 313 controls. Cases with high myopia were defined by spherical equivalent ≤ -8 dioptres and emmetropic controls by spherical equivalent within ±1.00 dioptre for both eyes. Manual candidate gene selection from the MYP6 locus was supported by objective in silico prioritization. DNA samples of discovery sample set were genotyped for 178 tagging single nucleotide polymorphisms (SNPs) from 26 genes. For replication, 25 SNPs (tagging or located at predicted transcription factor or microRNA binding sites) from 4 genes were subsequently examined using the replication sample set. Fisher P value was calculated for all SNPs and overall association results were summarized by meta-analysis. Based on initial and replication studies, rs2009066 located in the crystallin beta A4 (CRYBA4) gene was identified to be the most significantly associated with high myopia (initial study Pâ=â0.02; replication study Pâ=â1.88e-4; meta-analysis:
Pâ=â1.54e-5) among all the SNPs tested. The association result survived correction for multiple comparisons. Under the allelic genetic model for the combined sample set, the odds ratio of the minor allele G was 1.41 (95% confidence intervals, 1.21-1.64). CONCLUSIONS/SIGNIFICANCE:
A novel susceptibility gene (CRYBA4) was discovered for high myopia. Our study also signified the potential importance of appropriate gene prioritization in candidate selection.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Cadeia A de beta-Cristalina
/
Ligação Genética
/
Miopia
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
/
Systematic_reviews
Limite:
Adult
/
Female
/
Humans
/
Male
País/Região como assunto:
Asia
Idioma:
En
Revista:
PLoS One
Assunto da revista:
CIENCIA
/
MEDICINA
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
China