466-P: Exploration of Single Nucleotide Polymorphisms Associated with Small-Fiber Neuropathy

• Published in: Diabetes (New York, N.Y.) Vol. 74; no. Supplement_1; p. 1
• Main Authors: MIZUKAMI, HIROKI, OGASAWARA, SAORI, WANG, ZHENCHAO
• Format: Journal Article
• Language: English
• Published: New York American Diabetes Association 20.06.2025
• Subjects: Association analysis; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetic neuropathy; Electrical stimuli; Genomic analysis; Hyperglycemia; Neuropathy; Polymorphism; Polyneuropathy; Single-nucleotide polymorphism
• ISSN: 0012-1797; 1939-327X
• DOI: 10.2337/db25-466-P

Introduction and Objective: Introduction & Objective: Small fiber neuropathy (SFN) is known to develop early in the course of diabetic polyneuropathy (DPN). It has been shown that single nucleotide polymorphisms (SNPs) are involved in DPN, but how SNPs correlate with SFN has not yet been investigated. In the present study, we explored the correlation in Japanese health check cohort. Methods: Methods: 906 participants, including 785 controls, 121 fasting hyperglycaemia (IFG) subjects and 76 type 2 diabetes subjects (DM), in the 2017 Iwaki Health Promotion Project were evaluated. Pain threshold reflecting SFN was evaluated by Pain Threshold Induced by Intra-epidermal Electrical Stimulation (PINT) method. The weakest stimulation value in the PINT test was defined as the PINT index. A PINT index of 0.15 mA or less was defined as a low PINT index group and others as a high PINT index group. Genomic association analysis (GWAS) was performed using extracted DNA to examine the SNPs by Japonica array. Results: RESULTS: PINT index was significantly increased in IFG compared to healthy subjects (0.21 ± 0.22 mA vs. 0.15 ± 0.13 mA, p < 0.01). In GWAS, the obtained p-values were plotted in Manhattan plots and quantile-quantile plots, which revealed 10 SNPs with log10(p) > 5. Among them, rs482912 was further studied. rs482912 was divided into CC variant (143 cases), CT variant (420 cases) and TT variant (343 cases), in which there were no significant differences in weight and metabolic parameters. PINT index was significantly lower in CC than in the others (CC: 0.13 ± 0.13 mA, CT: 0.14 ± 0.13 mA, TT: 0.17 ± 0.16 mA, p < 0.01, respectively). When restricted to diabetic patients, the PINT index was significantly lower in the CC group than in the other groups (CC: 0.07±0.02 mA, CT: 0.19 ± 0.18 mA, TT: 0.17 ± 0.12 mA, p < 0.01, respectively). Conclusion: CONCLUSION: The CC variant of rs482912 may have an suppressive effect on the deterioration of pain threshold evoked by type 2 diabetes.