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.
Pediatr Diabetes
; 23(1): 104-114, 2022 02.
Article
en En
| MEDLINE
| ID: mdl-34773353
ABSTRACT
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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Polimorfismo Genético
/
Aldehído Reductasa
/
Diabetes Mellitus Tipo 1
/
Neuropatías Diabéticas
/
Homocigoto
Tipo de estudio:
Etiology_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Child
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Pediatr Diabetes
Asunto de la revista:
ENDOCRINOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Grecia