TY - JOUR
TI - Homozygosity of the Z-2 polymorphic variant in the aldose reductase gene
promoter confers increased risk for neuropathy in children and
adolescents with Type 1 diabetes
AU - Kallinikou, Dimitra
AU - Tsentidis, Charalampos
AU - Kekou, Kyriaki and
AU - Katsalouli, Marina
AU - Louraki, Maria
AU - Kanaka-Gantenbein, Christina
AU - and Kanavakis, Emmanouil
AU - Karavanaki, Kyriaki
JO - Pediatric Diabetes
PY - 2022
VL - 23
TODO - 1
SP - 104-114
PB - Wiley
SN - 1399-543X, 1399-5448
TODO - 10.1111/pedi.13285
TODO - autonomous; neuropathy; peripheral; Type 1 diabetes
TODO - Background Diabetic neuropathy (DN) is the least recognized complication
of diabetes mellitus and may start early in the course of the disease.
Aldose reductase (AKR1B1) gene promoter Z-2/Z-2 polymorphism increases
the expression of AKR1B1 enzyme and may contribute to DN. Subjects We
evaluated 108 Type 1 diabetes (T1D) children and adolescents (mean +/-
SD age: 13.5 +/- 3.46 years, disease duration: 5.3 +/- 3.4 years) and
150 healthy controls (age: 11.9 +/- 2.7 years). Methods In both groups,
pupillary dilation (PD) in darkness, postural blood pressure test
(PBPT), and vibration sensation thresholds (VST) in upper and lower
limbs were estimated as indices of autonomic and peripheral neuropathy,
respectively. Nerve conduction studies (NCS) were performed in patients
as peripheral neuropathy index. The polymorphisms of AKR1B1 gene were
evaluated using microsatellite (AC)n sequence Z. Results PBPT, PD, and
VST impairments were more frequent in patient group compared with
controls, while 38.6% of patients exhibited NCS abnormality. Gender,
age, pubertal status, height, body mass index, diabetes duration, HbA1c,
and anti-GAD titers were associated with neuropathy indices in patients.
There was a strong correlation between PD and NCS in patients, while
homozygous patients for Z-2 AKR1B1 gene polymorphism had higher
prevalence of abnormal NCS (83.3% vs. 34.6%), PD (62.5% vs. 31.5%),
and PBPT values compared with heterozygous or negative patients.
Homozygous AKR1B1 status predicted PD, NCS, and PBPT variance, while PD,
VST, NCS, and PBPT parameters accurately discriminated homozygous AKR1B1
patients. Conclusions Impaired indices of peripheral and autonomic DN
were present in a significant proportion of young T1D patients. PD, VST,
NCS, and PBPT parameters were simultaneously associated with homozygous
state of AKR1B1 Z-2 gene polymorphism, implicating polyol metabolism
with both autonomic and peripheral neuropathies.
ER -