Association of markers at chromosome 15q14 in Chinese patients with moderate to high myopia

Abstract

Purpose: To investigate the association of two reported regions on chromosome 15 with moderate to high myopia in two Chinese cohorts from southern China.

Methods: Two candidate regions on 15q14 and 15q25 were selected based on reported association with refractive error in the literature. Five single nucleotide polymorphisms (SNPs) were genotyped in 300 university students with high myopia at Guangzhou and 308 without refractive error, and 96 university students of Chaoshan Chinese origin with moderate to high myopia and 96 without refractive error. Genotypes were evaluated using direct sequencing and analyzed with chi-square, Armitage trend, and Mantel-Haenszel tests, and regression analysis.

Results: Of the five SNPs screened, alleles of rs634990 and rs524952 in the 15q14 region showed evidence of allelic association with moderate to high myopia (p<8.81×10(-7) and p<1.57×10(-6), respectively) in the Guangzhou group, but not in the Chaoshan group. The SNPs at 15q25 did not show significant association in any group. Association of rs634990 and rs524952 were still significant when both groups were combined into a single analysis (p<1.66×10(-6) and p<2.72×10(-6), respectively), and for genotypic, additive, and dominant models.

Conclusions: This study confirms the significant association of rs634990 and rs524952 on chromosome 15q14 previously reported in European and Japanese populations with high myopia in the Guangzhou but not the Chaoshan Chinese populations, suggesting that genetic contributors to high myopia in the Chaoshan population might be different from other Chinese populations.

Figure 1

Distribution of refraction and axial length among high myopic and control individuals in the Guangzhou and Chaoshan myopia and unaffected groups. The spherical equivalent of each individual is shown on the abscissa while the axial length is shown on the ordinate axis. Although the control samples are similarly clustered around 0 D: and 23 mm, the Chaoshan myopic group includes individuals with spherical equivalents < −4.

Figure 2

Linkage disequilibrium of markers at chromosome 15q14 and chromosome 15q25 in the Guangzhou and Chaoshan populations. Linkage disequilibrium is shown as r². The chromosomal positions are rs634990 (35,006,073), rs524952 (35,005,886), rs8027411 (79,461,029), rs17175798 (79,463,960), and rs939658 (79,451,869) from GRCh37.p5, build 37.3. For reference, the 5′ end of RASGRF1 is at 79,383,215, the 5′ end of GOLGA8B is at 34,875,771, the 3′ end of ACTC1 is at 35,080,297, and the 3′ end of GJD2 is at 35,044,679; the loci are not included in the regions shown here.