Abstract
Background and Objective: Variations in the cytochrome P450, family 1, subfamily B, polypeptide 1 (CYP1B1) gene and mutations in the latent transforming growth factor beta binding protein 2 (LTBP2) gene cause autosomal recessive Primary Congenital Glaucoma (PCG). However, in India, only 45% of PCG patients harbor alterations in the CYP1B1 gene. The present study aimed to identify novel genetic variations contributing to unexplained PCG cases in India.Methods: 112 unrelated Indian PCG patients in whom neither chromosome carried a CYP1B1 or an LTBP2 mutation, and 106 matched controls, were recruited for this study. DNA isolated from each case and control was screened for a total of 906,600 single nucleotide polymorphism (SNP) loci using an Affymetrix 6.0 whole genome genotyping array. The marker data were first used for an association analysis followed by multiple test corrections, after an initial adjustment for population stratification. A second approach undertaken in this study was detection of regions of homozygosity (ROH) across all autosomes that are significantly found more often in cases than in normal controls.Results: Eleven SNPs in 5 genes and intergenic regions showed statistically significant association with PCG. These genes are neuronal growth regulator 1 (NEGR1) [1p31.1], glutamate receptor, ionotropic, kainate 4 (GRIK4) [11q22.3], plexin domain containing 2 (PLXDC2) [10p12.31], YY1 associated factor 2 (YAF2) [12q12] and copine IV (CPNE4) [3q22.1]. The results of the ROH analysis have indicated the presence of two regions of homozygosity that cover two important genes, namely kelch‐like family member 26 (KLHL26) [19p13.11] and teashirt zinc finger homeobox 2 (TSHZ2) [20q13.2].Conclusions: The present study has identified likely locations of new putative genes underlying PCG. These genes have previously not been associated with any type of glaucoma, but the products of these genes appear to be involved in pathways related to eye development and physiology.Grant Funding Source: Department of Biotechnology
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