The impact of GJA8 SNPs on susceptibility to age-related cataract

Xiaoning Yu,Hao Yang,Xiyuan Ping,Xin Zhang,Xiajing Tang,Xingchao Shentu,Yelei Tang,Yilei Cui

doi:10.1007/s00439-018-1945-5

Xiaoning Yu, Hao Yang + Show 6 more

Open Access

https://doi.org/10.1007/s00439-018-1945-5

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Abstract

The gap junction protein alpha 8 (GJA8) gene has been widely studied in human congenital cataracts. However, little is known about its relationship with age-related cataract (ARC). In this study, three GJA8-tagged single nucleotide polymorphisms related to an increased ARC risk were identified: rs2132397 for general ARC under both dominant and additive models; rs7541950 for general ARC under both recessive and additive models; and rs6657114 for cortical cataract under the recessive model. To uncover the underlying mechanisms, this study also sought to explore whether GJA8 is involved in the autophagy process in human lens epithelial cells. The results showed that GJA8 may participate in autophagy to maintain the intracellular environment, which may be a novel mechanism for cataract formation induced by GJA8. In conclusion, this study identified the genetic susceptibility of GJA8 polymorphisms on ARC and provides new clues for fully understanding the pathological mechanism of GJA8 variants in affecting lens opacity.

Highlights

Cataracts are the leading cause of blindness and a major cause of vision impairment worldwide (Bourne et al 2013; Congdon et al 2003), with age-related cataract (ARC) being the most common type (Klein et al 1992, Su et al 2013)
As the alteration of the autophagy-related proteins LC3 and P62 in gap junction protein alpha 8 (GJA8)-overexpressed human lens epithelial (HLE) cells was detected, this study explores whether GJA8 participates in the autophagy process in the lens
The GJA8 protein is the major component of gap junction channels and hemichannels in the lens (Beyer et al 2013; Goodenough 1992)

Summary

Introduction

Cataracts are the leading cause of blindness and a major cause of vision impairment worldwide (Bourne et al 2013; Congdon et al 2003), with age-related cataract (ARC) being the most common type (Klein et al 1992, Su et al 2013). The precise etiology of ARC is not yet fully understood, but it is widely accepted that genetic factors play a vital role in the formation of ARC (Su et al 2013). Studies of twins have implicated that the broad sense heritability is 58% for the cortical subtype of ACR and 48% for the nuclear subtype of ARC (Hammond et al 2000, 2001). Genetic variations may be directly involved in the development of ARC or may increase lens susceptibility to environmental risk factors (Hammond et al 2001).

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