A PAX6 gene polymorphism is associated with genetic predisposition to extreme myopia

Abstract

Purpose The PAX6 gene is a homeobox gene involved in oculogenesis, ocular growth, and form-deprivation myopia. Our aim was to determine whether PAX6 polymorphism at position À12 of intron 9 (IVS9-12C to T, rs667773) is associated with high myopia in Chinese Taiwanese. Methods This case-control study compared a study group (n ¼ 188) with high myopia whose spherical equivalent was greater than À6.0 D with a control group (n ¼ 85) whose spherical equivalent was less than À0.5 D. Genotyping of IVS9-12C to T was conducted by restriction fragment length polymorphism analysis, and results were compared for the two groups. Results No significant difference in genotype and allelic frequency at this position between the study and control groups was detected. However, there was a significantly higher frequency of the CC genotype in extremely myopic (greater than À10 D) patients (Po0.001, odds ratio (OR ¼ 5.265), confidence interval (CI ¼ 2.0342-13.626)). Furthermore, there was a higher frequency of the C allele in the extreme myopia group than in the control group (P ¼ 0.002, OR ¼ 3.73, CI ¼ 1.57-8.81). Conclusions The elevated frequency of the CC genotype within the extreme myopia group indicated that the CC genotype could act as a genetic marker, identifying patients predisposed to develop extreme myopia. Varied expression of this genotype may contribute to the genetic predisposition to high myopia in Chinese Taiwanese.

A Functional Polymorphism at 3′UTR of thePAX6Gene May Confer Risk for Extreme Myopia in the Chinese

“…The present study demonstrates that a novel functional SNP at PAX6 may influence an individual's susceptibility to extreme myopia. Our finding for the PAX6 gene is consistent with two previous reports on high 16,24 and extreme myopia 15 in the Chinese population.…”

“…When there is no evidence of dominance, we prefer to not collapse heterozygotes with minor homozygotes unless the number of minor homozygotes is too small. Because the genetic effect may be more prominent for extreme myopia as indicated by a previous study, 15 we also conducted exploratory analyses by reclassifying cases with different refractive errors.…”

Association ofPAX6Polymorphisms with High Myopia in Han Chinese Nuclear Families

“…67 More interesting, the researchers in Taiwan reported strong association of extremely high myopia with PAX6 in a small case-control sample, whereas no association was found if the analysis also included subjects with less extreme myopia. 68 Of interest, the positive SNP (rs667773) reported in their study was also located in the 3Ј region of the PAX6 gene (intron 9), where potential variants responsible for susceptibility to high myopia might exist as discussed earlier. Therefore, we also tested SNP rs667773 in our high-myopia samples.…”

“…Two studies (one American and one British) reported negative association of PAX6 with common myopia, 65,66 whereas studies in Australian and Taiwan Chinese populations suggested association for PAX6 with high myopia. 67,68 It is not surprising that the conclusions of these recent reports are equivocal due to the complex etiology of myopia. In particular, the researchers in Australia reported association of some specific mutations in the PAX6 gene with highly myopic subjects.…”

Association of 15q14 and 15q25 with High Myopia in Japanese

“…[32][33][34] In addition, many candidate genes associated with high myopia have been reported. [35][36][37][38][39][40][41][42][43] However, most of these associated candidate genes have been negated by subsequent studies, and no genes have yet been identified that are consistently responsible for either common or high myopia.…”