Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis

Hidefumi Ruike

doi:10.1016/j.nbd.2026.107546

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis

2026-07-27

0

OA

AI

H

Hidefumi Ruike

H

Hiroki Mizukami *

Z

Zhenchao Wang

H

Hanae Kushibiki

M

Mizuri Ishida

S

Sho Osonoi

T

Takefusa Tarusawa

T

Takanori Sasaki

T

Tu Yi

S

Saori Ogasawara

A

Akiko Itaya

A

Atsumi Abe

G

Gentaro Kumagai

Y

Y. Tamada

Y

Yukihiro Fujita

T

Tatsuya Mikami

K

Ken Itoh

Y

Yasuyuki Ishibashi

K

Kenichi Hakamada

K

Koich Murashita

DOI：10.1016/j.nbd.2026.107546

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Abstract

En 中文

• A LAMP3 missense variant is associated with pain thresholds in diabetic polyneuropathy. • rs482912 CC genotype is linked to lower pain thresholds in dysglycaemia and obesity. • LAMP3+ dermal dendritic cells show inflammatory and nociception-related pathways. • Genotype-dependent skin immune cell differences occur without epidermal nerve fiber density. • Early sensory changes may reflect neuroimmune-mechanisms preceding axonal loss.

Keywords:

Pain threshold

Diabetic polyneuropathy

Small Fiber neuropathy

Single nucleotide polymorphism

LAMP3

ATR

Achilles tendon reflex

BW

body weight

BMI

body mass index

BUN

blood urea nitrogen

Cr

creatinine

dBP

diastolic blood pressure

DC

dendritic cell

DPN

diabetic polyneuropathy

fat

percent body fat

FBG

fasting blood glucose

FDR

false discovery rate

F-IRI

fasting immunoreactive insulin

GO

Gene Ontology

GSEA

Gene Set Enrichment Analysis

GWAS

genome-wide association study

HbA1c

glycated hemoglobin A1c

HDL-C

high-density lipoprotein cholesterol

HOMA-β

homeostatic model assessment of beta-cell function

HOMA-IR

homeostatic model assessment of insulin resistance

hs-CRP

high-sensitivity C-reactive protein

IENFD

intraepidermal nerve fiber density

IES

intraepidermal electrical stimulation

IFG

impaired fasting glucose

IHPP

Iwaki Health Promotion Project

IL-6

interleukin-6

LDL-C

low-density lipoprotein cholesterol

logFC

log fold change

mregDCs

mature dendritic cells enriched in immunoregulatory molecules

NES

normalized enrichment score

PINT

pain threshold from intraepidermal electrical stimulation

sBP

systolic blood pressure

scRNA-seq

single-cell RNA sequencing

SFN

small fiber neuropathy

SNPs

single nucleotide polymorphisms

TC

total cholesterol

TG

triglycerides

UMAP

Uniform Manifold Approximation and Projection

8-OHdG

8-hydroxy-2′-deoxyguanosine

Peripheral pain threshold, glycaemic status, and LAMP3 genetic variation: A community-based analysis

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