Association Study Of UMODL1Gene Polymorphisms With High Myopia In A Han Chinese Population

Purpose:The uromodulin-like1(UMODL1) gene was found to be associated with high myopia in Japanese. This study aimed to investigate this gene for association with high myopia in Chinese.Methods:Case-control association study was used in this study. Two groups of unrelated Han Chinese from Hong Kong were recruited using the same criteria:Sample Set1comprising356controls (spherical equivalent, SE, within±1.00diopter or D) and356cases (SE<-8.00D), and Sample Set2comprising394controls and526cases. All of the blood samples were performed DNA extraction. Fifty-nine tag single nucleotide polymorphisms (SNPs) were selected based on HapMap project of CHB database and genotyped for Sample Set1in the initial association study. Multiple primer-extension (PE) coupled with MALDI-TOF MS, PCR-RFLP, PE-DHPLC technologies were used for SNP genotyping. Four SNPs (rs220168, rs220170, rs11911271and rs3819142) were followed up with Sample Set2. Plink software was used for the sigle-marker association analyses under five genetic models (allelic, genotypic, additive, dominant and recessive). Haplotype association analyses were performed with three methods:LD-block-based method by Haploview, exhaustive variable-sized sliding window strategy by Plink, and localized haplotype clustering approach by Beagle. Multiple testing was corrected by10,000permutations to generate empirical P values (Pemp)-Secondary phenotypes were also analyzed for association with genotypes using the SPREG2.0. software followed by the false discovery rate (FDR) multiple comparisons correction.Results:In the initial association study, single-marker analysis did not reveal any significant differences between cases and controls of the57SNPs. The other two SNPs (rsl571737and rs220279) were excluded form the analyses because they were not in Hardy-Weinberg equilibrium (HWE). However, haplotype GCT for markers rs220168-rs220170-rs11911271showed marginal significance (P=0.0015; SE≤-12.00D for cases), but could not be replicated in the follow-up study.In contrast, non-synonymous SNP rs3819142was associated with high myopia (SE<-10.00D) in the follow-up study, but could not be confirmed using combined sample set (Sample Set1and Sample Set2). The SNP rs2839471, positive in the original Japanese study, gave negative results in all our analyses.Secondary phenotype analysis indicated that allele C of rs220120was associated with anterior chamber depth (P=0.001, adjusted P=0.046). The regression coefficient was-0.066(95%CI:-0.104to-0.027). The association signal was stronger when cases defined by SE≤-10.00D (P=0.0003, adjusted P=0.019).Conclusion:Common UMODL1polymorphisms were unlikely to be important in the genetic susceptibility to high myopia in Han Chinese, but might influence anterior chamber depth.