1. SNP located in an
- Author
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Lana, Verkuil, Ian, Danford, Maxwell, Pistilli, David W, Collins, Harini V, Gudiseva, Ben T, Trachtman, Jie, He, Sonika, Rathi, Naqi, Haider, Gui-Shuang, Ying, Venkata R M, Chavali, and Joan Marie, O'Brien
- Subjects
Male ,primary open-angle glaucoma ,genetic structures ,Genotyping Techniques ,Electrophoretic Mobility Shift Assay ,Transfection ,Polymerase Chain Reaction ,Polymorphism, Single Nucleotide ,Alu Elements ,Trabecular Meshwork ,Humans ,genetics ,Intraocular Pressure ,Aged ,Aged, 80 and over ,AluJb repeat ,Middle Aged ,eye diseases ,Black or African American ,Laboratory Science ,HEK293 Cells ,TMCO1 ,Case-Control Studies ,Female ,pathology ,Calcium Channels ,Glaucoma, Open-Angle ,Plasmids - Abstract
Aims To determine the association of single nucleotide polymorphisms (SNPs) downstream from the TMCO1 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 AluJb repeat and seven SNPs, including rs4656461 near the TMCO1 gene, were PCR-Sanger sequenced from POAAGG cases (n=1537) and controls (n=1570). Association between POAG and SNPs near TMCO1 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 TMCO1 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
- Published
- 2018