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

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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00439-018-1945-5) contains supplementary material, which is available to authorized users.