Investigating the relationship between UMODL1 gene polymorphisms and high myopia: a case–control study in Chinese

BMC Medical Genetics

Shea Ping Yip¹  Yang-shun Gu³  Po Wah Ng²  Wai Yan Fung¹  Daniel WH Ho²  Maurice KH Yap²  Miao-miao Zhu² 

[1] Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China;Centre for Myopia Research, School of Optometry, The Hong Kong Polytechnic University, Hong Kong SAR, China;Department of Ophthalmology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China

关键词: Secondary phenotype;    Association study;    Single nucleotide polymorphism;    UMODL1;    High myopia;   

Others  :  1177822
DOI  :  10.1186/1471-2350-13-64

 received in 2012-02-09, accepted in 2012-07-27,  发布年份 2012

【 摘 要 】

Background

The 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

Two groups of unrelated Han Chinese from Hong Kong were recruited using the same criteria: Sample Set 1 comprising 356 controls (spherical equivalent, SE, within ±1 diopter or D) and 356 cases (SE ≤ −8D), and Sample Set 2 comprising 394 controls and 526 cases. Fifty-nine tag single nucleotide polymorphisms (SNPs) were selected and genotyped for Sample Set 1. Four SNPs were followed up with Sample Set 2. Both single-marker and haplotype analyses were performed with cases defined by different SE thresholds. Secondary phenotypes were also analyzed for association with genotypes.

Results

Data filtering left 57 SNPs for analysis. Single-marker analysis did not reveal any significant differences between cases and controls in the initial study. However, haplotype GCT for markers rs220168-rs220170-rs11911271 showed marginal significance (empirical P = 0.076; SE ≤ −12D for cases), but could not be replicated in the follow-up study. In contrast, non-synonymous SNP rs3819142 was associated with high myopia (SE ≤ −10D) in the follow-up study, but could not be confirmed using Sample Set 1. The SNP rs2839471, positive in the original Japanese study, gave negative results in all our analyses. Exploratory analysis of secondary phenotypes indicated that allele C of rs220120 was associated with anterior chamber depth (adjusted P = 0.0460).

Conclusions

Common UMODL1 polymorphisms were unlikely to be important in the genetic susceptibility to high myopia in Han Chinese.

【 授权许可】

   
2012 Zhu et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1 .

【 参考文献 】

• [1]Saw SM, Gazzard G, Shih-Yen EC, Chua WH: Myopia and associated pathological complications. Ophthalmic Physiol Opt 2005, 25(5):381-391.
• [2]Vitale S, Sperduto RD, Ferris FL 3rd: Increased prevalence of myopia in the United States between 1971–1972 and 1999–2004. Arch Ophthalmol 2009, 127(12):1632-1639.
• [3]Kempen JH, Mitchell P, Lee KE, Tielsch JM, Broman AT, Taylor HR, Ikram MK, Congdon NG, O'Colmain BJ: The prevalence of refractive errors among adults in the United States, Western Europe, and Australia. Arch Ophthalmol 2004, 122(4):495-505.
• [4]Saw SM, Chua WH, Wu HM, Yap E, Chia KS, Stone RA: Myopia: gene-environment interaction. Ann Acad Med Singapore 2000, 29(3):290-297.
• [5]Tang WC, Yap MK, Yip SP: A review of current approaches to identifying human genes involved in myopia. Clin Exp Optom 2008, 91(1):4-22.
• [6]Dirani M, Chamberlain M, Garoufalis P, Chen C, Guymer RH, Baird PN: Refractive errors in twin studies. Twin Res Hum Genet 2006, 9(4):566-572.
• [7]Lopes MC, Andrew T, Carbonaro F, Spector TD, Hammond CJ: Estimating heritability and shared environmental effects for refractive error in twin and family studies. Invest Ophthalmol Vis Sci 2009, 50(1):126-131.
• [8]Nishizaki R, Ota M, Inoko H, Meguro A, Shiota T, Okada E, Mok J, Oka A, Ohno S, Mizuki N: New susceptibility locus for high myopia is linked to the uromodulin-like 1 (UMODL1) gene region on chromosome 21q22.3. Eye (Lond) 2009, 23(1):222-229.
• [9]Shibuya K, Nagamine K, Okui M, Ohsawa Y, Asakawa S, Minoshima S, Hase T, Kudoh J, Shimizu N: Initial characterization of an uromodulin-like 1 gene on human chromosome 21q22.3. Biochem Biophys Res Commun 2004, 319(4):1181-1189.
• [10]Di Schiavi E, Riano E, Heye B, Bazzicalupo P, Rugarli EI: UMODL1/Olfactorin is an extracellular membrane-bound molecule with a restricted spatial expression in olfactory and vomeronasal neurons. Eur J Neurosci 2005, 21(12):3291-3300.
• [11]EyeBrowse. http://eyebrowse.cit.nih.gov/ webcite
• [12]Zha Y, Leung KH, Lo KK, Fung WY, Ng PW, Shi MG, Yap MK, Yip SP: TGFB1 as a susceptibility gene for high myopia: a replication study with new findings. Arch Ophthalmol 2009, 127(4):541-548.
• [13]Barrett JC, Fry B, Maller J, Daly MJ: Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005, 21(2):263-265.
• [14]International HapMap Project. http://www.hapmap.org/ webcite
• [15]Oeth P, del Mistro G, Marnellos G, Shi T, van den Boom D: Qualitative and quantitative genotyping using single base primer extension coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MassARRAY). Methods Mol Biol 2009, 578:307-343.
• [16]Leung KH, Yip SP: Denaturing high-performance liquid chromatography. In Molecular Biomethods Handbook. 2nd edition. Edited by Walker JM, Rapley R. Humana Press, Totowa, NJ; 2008:89-106.
• [17]Leung KH, Yiu WC, Yap MK, Ng PW, Fung WY, Sham PC, Yip SP: Systematic investigation of the relationship between high myopia and polymorphisms of the MMP2, TIMP2 and TIMP3 genes by a DNA pooling approach. Invest Ophthalmol Vis Sci 2011, 52(6):3893-3900.
• [18]Yip SP, Leung KH, Ng PW, Fung WY, Sham PC, Yap MK: Evaluation of proteoglycan gene polymorphisms as risk factors in the genetic susceptibility to high myopia. Invest Ophthalmol Vis Sci 2011, 52(9):6396-403.
• [19]Ho DW, Yiu WC, Yap MK, Fung WY, Ng PW, Yip SP: Genotyping performance assessment of whole genome amplified DNA with respect to multiplexing level of assay and its period of storage. PLoS One 2011, 6(10):e26119.
• [20]Han W, Yip SP, Wang J, Yap MK: Using denaturing HPLC for SNP discovery and genotyping, and establishing the linkage disequilibrium pattern for the all-trans-retinol dehydrogenase (RDH8) gene. J Hum Genet 2004, 49(1):16-23.
• [21]Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D, Maller J, Sklar P, de Bakker PI, Daly MJ, Sham PC: PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007, 81(3):559-575.
• [22]Browning BL, Browning SR: Efficient multilocus association testing for whole genome association studies using localized haplotype clustering. Genet Epidemiol 2007, 31(5):365-375.
• [23]Browning SR, Browning BL: Rapid and accurate haplotype phasing and missing-data inference for whole-genome association studies by use of localized haplotype clustering. Am J Hum Genet 2007, 81(5):1084-1097.
• [24]BEAGLE software package. http://faculty.washington.edu/browning/beagle/beagle.html webcite
• [25]Lin DY, Zeng D: Proper analysis of secondary phenotype data in case–control association studies. Genet Epidemiol 2009, 33(3):256-265.
• [26]Storey JD, Tibshirani R: Statistical significance for genomewide studies. Proc Natl Acad Sci USA 2003, 100(16):9440-9445.
• [27]Schaid DJ: Evaluating associations of haplotypes with traits. Genet Epidemiol 2004, 27(4):348-364.
• [28]Guo Y, Li J, Bonham AJ, Wang Y, Deng H: Gains in power for exhaustive analyses of haplotypes using variable-sized sliding window strategy: a comparison of association-mapping strategies. Eur J Hum Genet 2009, 17(6):785-792.
• [29]Quanto software package. a. http://hydra.usc.edu/gxe/ webcite
• [30]Goh WS, Lam CS: Changes in refractive trends and optical components of Hong Kong Chinese aged 19–39 years. Ophthalmic Physiol Opt 1994, 14(4):378-382.
• [31]Wang Q, Gao Y, Wang P, Li S, Jia X, Xiao X, Guo X, Zhang Q: Replication study of significant single nucleotide polymorphisms associated with myopia from two genome-wide association studies. Mol Vis 2011, 17:3290-3299.
• [32]RevMan software package. http://ims.cochrane.org/revman/download webcite
• [33]Meng W, Butterworth J, Malecaze F, Calvas P: Axial length of myopia: a review of current research. Ophthalmologica 2011, 225(3):127-134.
• [34]Klein AP, Suktitipat B, Duggal P, Lee KE, Klein R, Bailey-Wilson JE, Klein BE: Heritability analysis of spherical equivalent, axial length, corneal curvature, and anterior chamber depth in the Beaver Dam Eye Study. Arch Ophthalmol 2009, 127(5):649-655.
• [35]He M, Hur YM, Zhang J, Ding X, Huang W, Wang D: Shared genetic determinant of axial length, anterior chamber depth, and angle opening distance: the Guangzhou Twin Eye Study. Invest Ophthalmol Vis Sci 2008, 49(11):4790-4794.
• [36]Biino G, Palmas MA, Corona C, Prodi D, Fanciulli M, Sulis R, Serra A, Fossarello M, Pirastu M: Ocular refraction: heritability and genome-wide search for eye morphometry traits in an isolated Sardinian population. Hum Genet 2005, 116(3):152-159.