NOVEL GENETIC VARIANTS ASSOCIATED WITH DIABETIC NEUROPATHY RISK IN TYPE 2 DIABETES: A WHOLE-EXOME SEQUENCING APPROACH
Hajdú Noémi
Rácz Károly Konzervatív Orvostudományi Tagozat
Dr. Fekete Andrea
SE Belgyógyászati és Onkológiai Klinika, Simonyi terem
2026-05-14 14:00:00
Anyagcsere betegségek
Dr. Lakatos Péter
Dr. Putz Zsuzsanna
Dr. Kis János Tibor
Dr. Sipter Emese
Dr. Karádi István
Dr. Nádas Judit
Dr. Nagy Géza
Diabetic polyneuropathy represents a serious complication that greatly influences both morbidity and mortality in people with diabetes. The condition shows considerable variability among individuals and does not always correspond to metabolic control, implying a potential pathogenic contribution of genetic factors. Despite the limited data currently available on biomarkers of diabetic polyneuropathy, multiple studies indicate the presence of genetic susceptibility.In our study, 24 long-standing type 2 diabetic patients with neuropathy and 24 without neuropathy underwent comprehensive neurological evaluation and whole-exome sequencing. Through this approach, we successfully identified genetic variants that may influence the risk of developing diabetic neuropathy.
We identified three variants in the titin gene out of which two were intronic SNPs (rs2291313 and rs4471922) and one as a missense mutation (rs922984). These variants seemed to have a role in the development of diabetic cardiomyopathy. Another genetic intronic variant that can elevate the risk of diabetic neuropathy is the rs6086563 in the phospholipase C-beta 1 (PLCβ1) gene through the altered inositol metabolism. In our study the rs4241602 SNP in the cyclin I gene seems to have a role in the development of allodynia. Also, rs2396295 and rs892204 which are intronic variants in the CDC34 gene suggest a connection between impaired endothelial progenitor cell function, vascular repair, and diabetic microvascular disease. Finally, the rs6682221 variant in the BTG2 gene, located within its upstream regulatory region, may play a role in neuronal regeneration through modulation of ID3 expression.
Overall, the synthesis of epidemiological, mechanistic, and genetic evidence highlights diabetic neuropathy as a multifactorial disorder, driven by both metabolic insults and genetic predisposition. Improved understanding of these pathways may support the development of targeted prevention strategies and novel therapeutic approaches.
