Journal of pediatric endocrinology & metabolism : JPEM · 2025
Prader-Willi syndrome gene expression profiling of obese and non-obese patients reveals transcriptional changes in CLEC4D and ANXA3.
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Yoon Ju Young, Shin Choong Ho, Choi Murim, Ko Jung Min, Lee Young Ah, Shim Kye Shik, Lee Jun, Yoo Suk Dong, Kim Minji, Yu Yeuni, Lee Joo Young, Kim Yun Hak, Cheon Chong Kun
Аннотация
OBJECTIVES: We aimed to characterize genetic alterations in Prader-Willi syndrome (PWS) using whole genome microarrays.
METHODS: We performed mRNA expression microarray analysis using RNA isolated from whole blood of 25 PWS patients and 25 age-matched controls. After preprocessing the data to reduce heterogeneity, differentially expressed genes (DEGs) between groups were identified using a linear regression model package. Reactome pathway analysis was performed for upregulated and downregulated genes using EnrichR. Correlations between gene expression levels and clinical factors were estimated using Spearman's rank correlation coefficient.
RESULTS: Of 21,488 probes examined in the microarray analysis, 4,156 were detected. Fifty-two genes had different expression levels in children with PWS compared with healthy controls (36 genes upregulated and 16 downregulated). Twelve genes were upregulated and 13 were downregulated in obese PWS patients compared with normal-weight PWS (NW-PWS) patients. The C-type lectin domain family 4 member D (CLEC4D) was upregulated in both PWS (vs. control) and obese-PWS (vs. NW-PWS) patients, and CLEC4D expression was also correlated with body mass index-standard deviation score in PWS patients. Among the genes upregulated in obese PWS vs. NW-PWS, Annexin A3 (ANXA3), potassium inwardly rectifying channel subfamily J member 15 (KCNJ15), and selenium binding protein 1 (SELENBP1) were upregulated in obese-control vs. NW-control. Gene ontology analysis revealed that upregulated DEGs were significantly enriched in biological processes, including pathways involved in myeloid dendritic cell activation associated with CLEC4D.
CONCLUSIONS: This study revealed differences in gene expression between obese and NW-PWS patients. The regulation of macrophage infiltration by CLEC4D suggests a possible mechanism associated with obesity-related complications in PWS.
METHODS: We performed mRNA expression microarray analysis using RNA isolated from whole blood of 25 PWS patients and 25 age-matched controls. After preprocessing the data to reduce heterogeneity, differentially expressed genes (DEGs) between groups were identified using a linear regression model package. Reactome pathway analysis was performed for upregulated and downregulated genes using EnrichR. Correlations between gene expression levels and clinical factors were estimated using Spearman's rank correlation coefficient.
RESULTS: Of 21,488 probes examined in the microarray analysis, 4,156 were detected. Fifty-two genes had different expression levels in children with PWS compared with healthy controls (36 genes upregulated and 16 downregulated). Twelve genes were upregulated and 13 were downregulated in obese PWS patients compared with normal-weight PWS (NW-PWS) patients. The C-type lectin domain family 4 member D (CLEC4D) was upregulated in both PWS (vs. control) and obese-PWS (vs. NW-PWS) patients, and CLEC4D expression was also correlated with body mass index-standard deviation score in PWS patients. Among the genes upregulated in obese PWS vs. NW-PWS, Annexin A3 (ANXA3), potassium inwardly rectifying channel subfamily J member 15 (KCNJ15), and selenium binding protein 1 (SELENBP1) were upregulated in obese-control vs. NW-control. Gene ontology analysis revealed that upregulated DEGs were significantly enriched in biological processes, including pathways involved in myeloid dendritic cell activation associated with CLEC4D.
CONCLUSIONS: This study revealed differences in gene expression between obese and NW-PWS patients. The regulation of macrophage infiltration by CLEC4D suggests a possible mechanism associated with obesity-related complications in PWS.