Dataset Information

Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population.

ABSTRACT: To investigate the association between high myopia (HM) and single nucleotide polymorphisms (SNPs) in the myocilin (MYOC), hepatocyte growth factor (HGF), hepatocyte growth factor receptor (MET), and aggrecan (ACAN) genes in a Han Chinese population.Sixteen SNPs were genotyped by the SNaPshot method in a subject group composed of 1052 HM patients and 1070 controls. Statistical analysis was performed to determine the association between the SNPs and the susceptibility of HM.Two SNPs (rs3784757 and rs1516794) in ACAN were significantly associated with HM (p=0.0334 and 0.0236, odds ratio [OR]=0.83 and 0.79, respectively). The risk haplotype CA and the protective haplotype TT, generated by rs3784757 and rs1516794, showed significant association with HM (p=0.0327 and 0.0304, OR=1.21 and 0.80, respectively). Two SNPs (rs38857 and rs10215153) in MET and one SNP (rs3784757) in ACAN showed significant association with HM (p=0.0064, 0.0113, and 0.0373; OR=4.14, 5.74 and 0.52; respectively) in the recessive model. None of the other SNPs showed significant association with HM.Our results suggested that genetic variants in ACAN and MET are associated with HM. Functional roles of ACAN and MET in the development of HM need to be further investigated.

SUBMITTER: Yang X

PROVIDER: S-EPMC4043249 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population.

Yang Xian X Liu Xiaoqi X Peng Jie J Zheng Hong H Lu Fang F Gong Bo B Zhao Guiqiu G Meng Yan Y Guan Hongzai H Ning Meizhen M Yang Zhenglin Z Shi Yi Y

Genetic testing and molecular biomarkers 20140425 6

<h4>Aim</h4>To investigate the association between high myopia (HM) and single nucleotide polymorphisms (SNPs) in the myocilin (MYOC), hepatocyte growth factor (HGF), hepatocyte growth factor receptor (MET), and aggrecan (ACAN) genes in a Han Chinese population.<h4>Methods</h4>Sixteen SNPs were genotyped by the SNaPshot method in a subject group composed of 1052 HM patients and 1070 controls. Statistical analysis was performed to determine the association between the SNPs and the susceptibility ...[more]

PMID: 24766640

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Project description:Background:Fibroblast growth factor 10 (FGF10) is implicated in the growth and development of the eye. Four singles nucleotide polymorphisms (SNPs) in the FGF10 gene (including rs1384449, rs339501, rs12517396 and rs10462070) were found to be associated with extreme myopia (EM, refractive error???-?10.0 diopters) in Japanese and Chinese Taiwan population. This case-control association study was conducted to explore the relationship between these four SNPs and high myopia in a western Chinese population. Methods:A total of 869 high myopia patients (HM, including 485 EM patients) and 899 healthy controls were recruited. These four SNPs were genotyped using the ABI SNaPshot method. Five genetic models (allelic, homozygous, heterozygous, dominant, and recessive) were applied to further evaluate the possible correlation between the SNPs and high myopia. The linkage-disequilibrium block (LD) structure was tested by Haploview Software. Results:In our study, no statistically significant differences were found between HM/EM patients and controls after Bonferroni multiple-correction (P?>?0.05) in the allele frequencies of these four SNPs in the FGF10 gene. We further found that rs12517396AA and rs10462070GG carriers showed a decreased risk of HM/EM compared with rs12517396AC?+?CC and rs10462070GA?+?AA carriers (P?=?0.045, OR?=?0.366; P?=?0.021, OR?=?0.131; P?=?0.03, OR?=?0.341; P?=?0.015, OR?=?0.122; respectively). Additionally, rs12517396AA and rs10462070GG carriers showed the same decreased risk of HM/EM compared with rs12517396CC and rs10462070AA carriers (P?=?0.048, OR?=?0.370; P?=?0.023, OR?=?0.133; P?=?0.032, OR?=?0.346; P?=?0.017, OR?=?0.126). However, these significant associations between rs12517396/rs10462070 and HM/EM disappeared after Bonferroni multiple-correction (P?>?0.05). Conclusion:Our findings indicate that rs12517396 and rs10462070 had marginal association with HM and EM. The other two common polymorphisms in FGF10 unlikely have significant effects in the genetic predisposition to HM/EM in western Chinese population. Further replication studies are needed to validate our findings in both animal models and human genetic epidemiologic studies.

Project description:PURPOSE: To test the association between myocilin gene (MYOC) polymorphisms and high myopia in Hong Kong Chinese by using family-based association study. METHODS: A total of 162 Chinese nuclear families, consisting of 557 members, were recruited from an optometry clinic. Each family had two parents and at least one offspring with high myopia (defined as -6.00D or less for both eyes). All offspring were healthy with no clinical evidence of syndromic disease and other ocular abnormality. Genotyping was performed for two MYOC microsatellites (NGA17 and NGA19) and five tag single nucleotide polymorphisms (SNPs) spreading across the gene. The genotype data were analyzed with Family-Based Association Test (FBAT) software to check linkage and association between the genetic markers and myopia, and with GenAssoc to generate case and pseudocontrol subjects for investigating main effects of genetic markers and calculating the genotype relative risks (GRR). RESULTS: FBAT analysis showed linkage and association with high myopia for two microsatellites and two SNPs under one to three genetic models after correction for multiple comparisons by false discovery rate. NGA17 at the promoter was significant under an additive model (p=0.0084), while NGA19 at the 3' flanking region showed significant results under both additive (p=0.0172) and dominant (p=0.0053) models. SNP rs2421853 (C>T) exhibited both linkage and association under additive (p=0.0009) and dominant/recessive (p=0.0041) models. SNP rs235858 (T>C) was also significant under additive (p=4.0E-6) and dominant/recessive (p=2.5E-5) models. Both SNPs were downstream of NGA19 at the 3' flanking region. Positive results for these SNPs were novel findings. A stepwise conditional logistic regression analysis of the case-pseudocontrol dataset generated by GenAssoc from the families showed that both SNPs could separately account for the association of NGA17 or NGA19, and that both SNPs contributed separate main effects to high myopia. For rs2421853 and with C/C as the reference genotype, the GRR increased from 1.678 for G/A to 2.738 for A/A (p=9.0E-4, global Wald test). For rs235858 and with G/G as the reference, the GRR increased 2.083 for G/A to 3.931 for A/A (p=2.0E-2, global Wald test). GRR estimates thus suggested an additive model for both SNPs, which was consistent with the finding that, of the three models tested, the additive model gave the lowest p values in FBAT analysis. CONCLUSIONS: Linkage and association was shown between the MYOC polymorphisms and high myopia in our family-based association study. The SNP rs235858 at the 3' flanking region showed the highest degree of confidence for association.

Project description:BackgroundOligozoospermia is one of the severe forms of idiopathic male infertility. However, its pathology is largely unknown, and few genetic factors have been defined. Our previous genome-wide association study (GWAS) has identified four risk loci for non-obstructive azoospermia (NOA).ObjectiveTo investigate the potentially functional genetic variants (including not only common variants, but also less-common and rare variants) of these loci on spermatogenic impairment, especially oligozoospermia.Design setting and participantsA total of 784 individuals with oligozoospermia and 592 healthy controls were recruited to this study from March 2004 and January 2011.MeasurementsWe conducted a two-stage study to explore the association between oligozoospermia and new makers near NOA risk loci. In the first stage, we used next generation sequencing (NGS) in 96 oligozoospermia cases and 96 healthy controls to screen oligozoospermia-susceptible genetic variants. Next, we validated these variants in a large cohort containing 688 cases and 496 controls by SNPscan for high-throughput Single Nucleotide Polymorphism (SNP) genotyping.Results and limitationsTotally, we observed seven oligozoospermia associated variants (rs3791185 and rs2232015 in PRMT6, rs146039840 and rs11046992 in Sox5, rs1129332 in PEX10, rs3197744 in SIRPA, rs1048055 in SIRPG) in the first stage. In the validation stage, rs3197744 in SIRPA and rs11046992 in Sox5 were associated with increased risk of oligozoospermia with an odds ratio (OR) of 4.62 (P ?=? 0.005, 95%CI 1.58-13.4) and 1.82 (P ?=? 0.005, 95%CI 1.01-1.64), respectively. Further investigation in larger populations and functional characterizations are needed to validate our findings.ConclusionsOur study provides evidence of independent oligozoospermia risk alleles driven by variants in the potentially functional regions of genes discovered by GWAS. Our findings suggest that integrating sequence data with large-scale genotyping will serve as an effective strategy for discovering risk alleles in the future.

Dataset Information

Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population.

Publications

Evaluation of MYOC, ACAN, HGF, and MET as candidate genes for high myopia in a Han Chinese population.

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