Association of Genes implicated in primary angle-closure Glaucoma and the ocular biometric parameters of anterior chamber depth and axial length in a northern Chinese population

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.

Association between axial length and HDL in children: a hospital-based cross-sectional study

“…On the other hand, Wnt signal transduction pathway plays a vital role in the development of the eye by the coreceptors [ 33 , 34 ]. It is well established that MFRP (membrane Frizzled-related protein) is connected to the Wnt binding cysteine-rich domain of the frizzled family of transmembrane proteins [ 35 ]. These proteins are competitive inhibitors of Wnt signaling, which is an important mechanism in the formation of the vertebrate eye.…”

Association of Single-Nucleotide Polymorphisms in <b><i>ABCC5</i></b> Gene with Primary Angle Closure Glaucoma and the Ocular Biometric Parameters in a Northern Chinese Population

“…A total of 1,220 unrelated Chinese individuals were recruited from the northern regions of China, including 500 PACG patients and 720 unaffected controls. The detailed ophthalmic examinations for every participant, and the inclusion and exclusion criteria as well as the protocol of genetic DNA extraction were identical to those in our previous study [13].…”

“…The comparisons of demographic characteristics between cases and controls and the correlations analyses between genotypes and ocular biometric parameters were implemented by SPSS software (version 17.5: SPSS Science, Chicago, IL, USA); the genetic association analyses were performed by PLINK (version 1.07; http://pngu.mgh.harvard.edu/∼purcell/plink/, in the public domain); the detailed statistical analysis methods were the same as our previous study [13]. The statistical power was evaluated by the Power and Sample Size Calculation (PS; version 3.1.232).…”