Juvenile idiopathic arthritis patients and their skeletal status: possible role of vitamin D receptor gene polymorphism

Abstract

We evaluated bone mineralization and metabolism changes related to vitamin D receptor (VDR) polymorphic genotypes in children with juvenile idiopathic arthritis. One hundred and ninety eight children (82 boys and 116 girls) were included in our study. Bone mineral density (BMD) was measured by lumbar spine DXA. Osteocalcin, CTX, parathyroid hormone, total and ionized calcium, inorganic phosphate, total alkaline phosphatase activity was utilized for assessment of bone metabolism. Molecular testing: TaqI (rs731236) and Cdx2 (rs11568820) polymorphisms of VDR were detected by RFLP. No differences in TaqI and Cdx2 haplotypes, genotypes and alleles distribution related with normal and low BMD (Zscore <-2SD) were found. Children with low linear growth (<10th percentile) had more allele T-contained genotypes of TagI VDR (p = 0.037), compare with medium or high linear growth children. Children with high linear growth (>90th percentile) had the highest frequency of allele A-contained genotypes (GA+AA) of Cdx2 VDR (p = 0.009). Girls with TT TaqI VDR, who never been treated by glucocorticoides had lower BMD-Zscore than C allele carriers (TT = -0.94SD [IQR: -2.1;-0.5], TC+CC = -0.62SD [IQR: -1.26;0.39], p = 0.03). Girls with Tanner I with TT had higher total and ionized Ca level than carriers of C allele (Ca: TT = 2.43 ± 0.15 mmol/l, TC+CC = 2.28 ± 0.2 mmol/l, p = 0.024; Ca(2+): TT = 1.15 ± 0.08 mmol/l, TC+CC = 1.06 ± 0.13 mmol/l, p = 0.026). Presence of TT genotype negatively correlated with BMD-Zscore (r = -0.28, p = 0.04), and positively with frequency of LBMD (r = 0.3, p = 0.037). Boy with GG Cdx2 genotype had lower total Ca (GG = 2.3 ± 0.17 mmol/l, GA+AA = 2.43 ± 0.17 mmol/l, p = 0.004) compare with carriers of A allele. Pubertal boys (Tanner IV-V) with GG had higher CTX (GG = 1.75 ± 0.11 ng/ml, GA+AA = 1.06 ± 0.07 ng/ml, p = 0.04. TT genotype of TaqI and GG genotype of Cdx2 VDR is a negative factor impact bone mineralization metabolism and linear growth.

Study of vitamin D status and vitamin D receptor polymorphisms in a cohort of Italian patients with juvenile idiopathic arthritis

“…It is suspected that a reduction of vitamin D level/activity favours the development of JIA and the maintenance of the active status of the disease. To date, only three studies 22 – 24 have analysed VDR polymorphisms in JIA patients, principally in relation to bone status 23 , 24 .…”

“…Kostik et al 24 recently investigated the role of Cdx2 and TaqI polymorphisms of the VDR gene in 192 JIA patients regarding bone status and metabolism (measured by lumbar spine DXA and biomarkers of bone turnover, respectively) and linear growth. The A allele of the Cdx2 polymorphism was significantly more frequent in individuals with higher calcium absorption and high linear growth and the TT genotype of TaqI polymorphism was associated with lower BMD.…”

Role of TaqI-Genetic Polymorphism of Vitamin D Receptor Gene in Bone Metabolism in Children with Inflammatory Bowel Disease

“…У мальчиков и девочек с генотипом TT TaqI гена VDR в периоде полового созревания, не получавших кортикостероиды, значения BMD были ниже нормы, что позволяет рассматривать поли-морфный ТТ-генотип как фактор риска нарушений минерализации [3]. Присутствие TT-генотипа отри- Примечание: ВЗК -воспалительные заболевания кишечника; СКТ -С-концевые телопептиды; ОК -остеокальцин; вгн -верхняя граница нормы Таблица 5 сравнительная характеристика параметров костного метаболизма между пациентами с воспалительными заболеваниями кишечника и группой контроля в зависимости от TaqI-полиморфных генотипов VDR цательно коррелировало с МПК (r = -0,28, p = 0,04) и положительно с частотой низкой МПК (r = 0,3, p = 0,037) [17]. При изучении роли пяти полиморф-ных генотипов гена VDR (BsmI, FokI, ApaI, TaqI и Cdx2) у 90 детей с инсулин-зависимым сахарным диабетом не было выявлено влияния указанных генотипов на костный метаболизм и минерализа-цию [16].…”