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Abstract #80621 Published in IGR 20-3
SNP located in an repeat downstream of rs4657473, is protective for POAG in African Americans
Verkuil L; Danford I; Pistilli M; Collins DW; Gudiseva HV; Trachtman BT; He J; Rathi S; Haider N; Ying GS; Chavali VRM; O'Brien JMBritish Journal of Ophthalmology 2019; 103: 1530-1536
AIMS: To determine the association of single nucleotide polymorphisms (SNPs) downstream from the gene with primary open-angle glaucoma (POAG) in African Americans (AA). METHODS: AA subjects were recruited for the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study from the Scheie Eye Institute and its satellite sites in Philadelphia. A region containing an repeat and seven SNPs, including rs4656461 near the gene, were PCR-Sanger sequenced from POAAGG cases (n=1537) and controls (n=1570). Association between POAG and SNPs near was investigated by logistic regression analysis. Phenotypic trait associations with these SNPs were assessed by analysis of variance. Electrophoretic mobility shift assay (EMSA) was performed to assess the affinity of human T-box 5 (TBX5) protein for a predicted binding motif in the region. Dual Luciferase assays were performed by transfecting recombinant plasmids containing the region surrounding the above SNPs in HEK293T and trabecular meshwork cells. RESULTS: The SNP rs4657473 (C>T) was associated with POAG; the TT genotype was protective (OR 0.20, 95% CI 0.09 to 0.42; p<0.001). No significant associations were found between the variants and phenotypic traits. EMSA confirmed the affinity of TBX5 for a predicted binding motif containing SNP rs4657475. Luciferase assays demonstrated a regulatory function for the genomic region around SNP rs4656561, located within repeat. CONCLUSION: Our results demonstrate that a SNP downstream of TMCO1, rs4657473, is associated with POAG in an AA population. Our studies suggest a regulatory role for the previously POAG-associated locus near the gene that may affect gene expression.
Ophthalmology, Scheie Eye Institute, Philadelphia, Pennsylvania, USA.
Full articleClassification:
3.4.2 Gene studies (Part of: 3 Laboratory methods > 3.4 Molecular genetics)