Association Between Progranulin and Gaucher Disease

• Published in: EBioMedicine 2016-09, Vol.11 (C), p.127-137
• Main Authors: Jian, Jinlong, Zhao, Shuai, Tian, Qing-Yun, Liu, Helen, Zhao, Yunpeng, Chen, Wen-Chi, Grunig, Gabriele, Torres, Paola A., Wang, Betty C., Zeng, Bai, Pastores, Gregory, Tang, Wei, Sun, Ying, Grabowski, Gregory A., Kong, Max Xiangtian, Wang, Guilin, Chen, Ying, Liang, Fengxia, Overkleeft, Herman S., Saunders-Pullman, Rachel, Chan, Gerald L., Liu, Chuan-ju
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alleles; Animals; Case-Control Studies; Disease Models, Animal; Enzyme Activation; Female; Gaucher disease; Gaucher Disease - blood; Gaucher Disease - diagnosis; Gaucher Disease - genetics; Gene Frequency; Genetic Association Studies; Genotype; Humans; Intercellular Signaling Peptides and Proteins - blood; Intercellular Signaling Peptides and Proteins - genetics; Lysosomal storage diseases; Lysosomes - metabolism; Male; Mice; Mice, Knockout; Middle Aged; Mutation; Phenotype; Polymorphism, Single Nucleotide; Progranulin; Protein Transport; Research Paper; β-Glucocerebrosidase
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2016.08.004

Gaucher disease (GD) is a genetic disease caused by mutations in the GBA1 gene which result in reduced enzymatic activity of β-glucocerebrosidase (GCase). This study identified the progranulin (PGRN) gene (GRN) as another gene associated with GD. Serum levels of PGRN were measured from 115 GD patients and 99 healthy controls, whole GRN gene from 40 GD patients was sequenced, and the genotyping of 4 SNPs identified in GD patients was performed in 161 GD and 142 healthy control samples. Development of GD in PGRN-deficient mice was characterized, and the therapeutic effect of rPGRN on GD analyzed. Serum PGRN levels were significantly lower in GD patients (96.65±53.45ng/ml) than those in healthy controls of the general population (164.99±43.16ng/ml, p