Association of long noncoding RNA MEG3 genetic variants with the risk of diabetic neuropathy

Diabetic neuropathy (DN), known to result from an interplay of acquired and genetic factors, is a common comorbidity of diabetes characterized by various forms of nerve damage. Maternally expressed gene 3 (MEG3) is an imprinted, non-coding RNA gene originally identified as a tumor suppressor. Recently, dysregulation of MEG3 levels was also observed in various neurodegenerative diseases. In this study, we aimed to investigate the potential association of MEG3 gene polymorphisms with the risk for DN through genotyping five single-nucleotide polymorphisms (SNPs) of MEG3 gene (rs4081134, rs10144253, rs7158663, rs3087918, and rs11160608) between 712 DN patients and 820 controls (diabetic individuals without neuropathic conditions). Our survey revealed a gender-specific association of rs7158663 with DN. We found that rs7158663 of MEG3 gene was associated with an increased risk for DN in diabetic women (GA vs GG, AOR=1.604, p=0.005; GA+AA vs GG, AOR=1.547, p=0.007). Nevertheless, such genetic association was particularly seen in women but not detected in diabetic males. Moreover, a higher level of LDL-cholesterol was noted in female DN patients who carry homozygous major allele of rs7158663 (GG) than in those bearing at least one minor allele (GA+AA) (p=0.016), suggesting an effect of rs7158663 on modulating lipoprotein levels. Taken together, our results demonstrate a link of MEG3 gene variants with dyslipidemia and neuropathic conditions in diabetic patients in a gender-specific manner.