Gitelman综合征患儿基因变异的类型与骨代谢标志物及骨微结构的相关性

Correlation between genotypes with metabolic markers and microstructure of bones in children with Gitelman syndrome

目的探讨Gitelman综合征(Gitelman syndrome,GS)患儿基因型与骨代谢标志物、骨微结构的相关性。方法选择15例患儿作为GS组,并选择同期体检的10名健康志愿者作为对照组,获取两组的基线资料、骨代谢标志物(包括全段甲状旁腺素、碱性磷酸酶、骨钙素、Ⅰ型前胶原氨基端前肽、β-胶原降解产物、25羟维生素D)、高分辨外周骨定量CT指标(体积骨密度、骨微结构指标);同时采集外周血样进行检测,明确其基因型和变异类型。结果GS组体积骨密度、骨几何学及骨微结构参数均优于健康组(P<0.05)。有9例患儿携带SLC12A3基因变异,而10名健康者均未查见SLC12A3变异。结论GS患儿的遗传表型受多种变异类型的相互作用,但高频变异基因导致的表型并无特异性,此外基因变异类型与骨骼微结构存在一定的关系。

Objective To explore the correlation between the genotypes and metabolic markers and microstructure of bones in children with Gitelman syndrome(GS).Methods For 15 children with GS and 10 healthy individuals,baseline data and bone metabolic markers including parathyroid hormone,alkaline phosphatase,osteocalcin,N-terminal propeptide of typeⅠprocollagen,βisomer of the C-terminal telopeptide of typeⅠcollagen and 25-hydroxyvitamin D,high-resolution peripheral quantitative computed tomography indicators(volumetric bone mineral density,bone microstructure indicators)were collected.Genetic testing was carried out to determine their genotypes.Results The volumetric bone mineral density,bone geometry and bone microstructure parameters of the GS group were better than those of the healthy controls(P<0.05).Variants of the SLC12A3gene were identified in 9 of the 15 patients but none of the 10 healthy controls.Conclusion The phenotype of GS children is influenced by the interaction of genetic variants,though the phenotype associated with high frequency mutations showed no specificity.There is also a correlation between their genotype and the bone microstructure.