Abstract
BackgroundThe membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; also, the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL. The present study investigated the association of single nucleotide polymorphisms (SNPs) in ZNRF3, HGF and MFRP with PACG in a northern Chinese population, as well as the association of these SNPs with the ocular biometric parameters of anterior chamber depth (ACD) and AL.MethodsA total of 500 PACG patients and 720 controls were recruited. All individuals were genotyped for 12 SNPs in three genes (rs7290117, rs2179129, rs4823006 and rs3178915 in ZNRF3; rs5745718, rs12536657, rs12540393, rs17427817 and rs3735520 in HGF, rs2510143, rs36015759 and rs3814762 in MFRP) using an improved multiplex ligation detection reaction (iMLDR) technique. Genotypic distribution was analyzed for Hardy-Weinberg equilibrium. Differences in the allelic and genotypic frequencies were evaluated and adjusted by age and sex. Linkage disequilibrium (LD) patterns were tested and haplotype analysis was conducted by a logistic regression model. Generalized estimation equation (GEE) analysis was conducted using SPSS for primary association testing between genotypes and ocular biometric parameters. Bonferroni corrections for multiple comparisons were performed, and the statistical power was calculated by power and sample size calculations.ResultsThe rs7290117 SNP in ZNRF3 was significantly associated with the AL, with a p-value of 0.002. We did not observe any significant associations between the SNPs and PACG or ACD. In a stratification analysis by ethnicity, rs12540393 and rs17427817 in HGF showed a nominal association with PACG in the Hui cohort, although significance was lost after correction.ConclusionsThe present study suggests rs7290117 in ZNRF3 may be involved in the regulation of AL, though our results do not support a contribution of the SNPs we tested in ZNRF3, HGF and MFRP to PACG in northern Chinese people. Further studies in a larger population are warranted to confirm this conclusion.
Highlights
The membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL
The present study suggests rs7290117 in ZNRF3 may be involved in the regulation of AL, though our results do not support a contribution of the single nucleotide polymorphisms (SNPs) we tested in ZNRF3, HGF and MFRP to PACG in northern Chinese people
The genotyping call rates for the 12 SNPs in both case and control groups were more than 99% and their allele distributions were within Hardy-Weinberg equilibrium (HWE) (P > 0.05) (Table 2)
Summary
The membrane frizzled-related protein (MFRP) gene is involved in axial length (AL) regulation and MFRP mutations cause nanophthalmos; the hepatocyte growth factor (HGF) gene is reported to result in morphologic changes of the anterior segment and abnormal aqueous regulation that increases the risk of primary angle-closure glaucoma (PACG), while the zinc ring finger 3 (ZNRF3) gene is associated with AL. 2 genome-wide association studies (GWAS) on PACG have been conducted and 8 genetic loci showed strong associations with the disease [7, 8]. In another GWAS on anterior chamber depth (ACD), the rs1401999 locus in the ABCC5 gene was found to be associated with PACG [9]. These genes only partly explain the genetic predisposition to PACG
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