Common Variants in the COL4A4 Gene Confer Susceptibility to Lattice Degeneration of the Retina

Abstract

Lattice degeneration of the retina is a vitreoretinal disorder characterized by a visible fundus lesion predisposing the patient to retinal tears and detachment. The etiology of this degeneration is still uncertain, but it is likely that both genetic and environmental factors play important roles in its development. To identify genetic susceptibility regions for lattice degeneration of the retina, we performed a genome-wide association study (GWAS) using a dense panel of 23,465 microsatellite markers covering the entire human genome. This GWAS in a Japanese cohort (294 patients with lattice degeneration and 294 controls) led to the identification of one microsatellite locus, D2S0276i, in the collagen type IV alpha 4 (COL4A4) gene on chromosome 2q36.3. To validate the significance of this observation, we evaluated the D2S0276i region in the GWAS cohort and in an independent Japanese cohort (280 patients and 314 controls) using D2S0276i and 47 single nucleotide polymorphisms covering the region. The strong associations were observed in D2S0276i and rs7558081 in the COL4A4 gene (Pc = 5.8×10−6, OR = 0.63 and Pc = 1.0×10−5, OR = 0.69 in a total of 574 patients and 608 controls, respectively). Our findings suggest that variants in the COL4A4 gene may contribute to the development of lattice degeneration of the retina.

Posterior segment conditions associated with myopia and high myopia

“…87 The exact mechanism underlying lattice degeneration remains unknown but an abnormality in the development of internal limiting membrane, choroidal abnormalities or vitreoretinal traction is considered to be some of the causes. 88 It is important to note that retinal tears can occur following traction from PVD. 89 Also, atrophic retinal holes within the lattice may cause a localised retinal detachment.…”

“…Other features that may be present include lattice‐like lines, alterations of retinal pigment, areas of thinning and atrophic retinal holes 2003. The exact mechanism underlying lattice degeneration remains unknown but an abnormality in the development of internal limiting membrane, choroidal abnormalities or vitreoretinal traction is considered to be some of the causes 2012. It is important to note that retinal tears can occur following traction from PVD 2018.…”

Lattice degeneration imaging with optical coherence tomography angiography

“…To date there are no comprehensive genetic studies on lattice degeneration, but changes in collagen A expression may contribute to this condition. 9 …”

An analytical enrichment‐based review of structural genetic studies on keratoconus

“…75 It is well represented that mutations in miR-184 are also responsible for congenital cataracts and corneal abnormalities 76 and endothelial dystrophy, iris hypoplasia, congenital cataract, and stromal thinning (EDICT syndrome). 85 DNA sequencing showed a total 84 singlenucleotide variations in patients, including 18 nonsynonymous variations and two novel frame-shift mutations.…”

“…COL4A4 gene product is a subunit of type IV collagen and its mutations are reported to be associated with Alport syndrome, a hereditary nephritis, which is often associated with deafness and/or ocular abnormalities, 84 and lattice degeneration of the retina. 85…”