Genome-wide methylation study of whole blood cells DNA in men with congenital hypopituitarism disease

Fang,Xuqian; Chen,Changqiang; Cai,Jialin; Xiang,Enfei; Li,Jingquan; Chen,Peizhan

doi:10.3892/ijmm.2018.3945

Genome-wide methylation study of whole blood cells DNA in men with congenital hypopituitarism disease

Authors:
- Xuqian Fang
- Changqiang Chen
- Jialin Cai
- Enfei Xiang
- Jingquan Li
- Peizhan Chen
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Affiliations: Department of Pathology, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China, Department of Clinical Medicine, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China, Clinical Research Center, Ruijin Hospital North, Shanghai Jiao Tong University School of Medicine, Shanghai 201821, P.R. China, School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, P.R. China
Published online on: October 22, 2018 https://doi.org/10.3892/ijmm.2018.3945
Pages: 155-166
Copyright: © Fang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Congenital hypopituitarism (CH) is a relatively rare disease that is characterized by the deficiency of one or more hormones secreted by the pituitary gland, which leads to metabolic disorders, amenorrhea and infertility. However, the underlying molecular mechanisms of CH have not yet been fully elucidated. The present study evaluated the genome‑wide methylation level of whole blood DNA in 12 patients with CH and 12 age‑matched controls using Illumina Human Methylation 450 array, in order to determine the roles of epigenetic regulation in the pathogenesis of CH. The results demonstrated that the methylation levels of 51 CpG sites were significantly different between the patients with CH and the controls. Functional enrichment analysis identified that the aberrant methylated genes were enriched in gene sets associated with metabolic or cellular process, immune system process and reproduction. In addition, two CpG sites on genes LIM domain kinase 2 (LIMK2) and piwi‑like RNA‑mediated gene silencing 2 (PIWIL2), which are involved in spermatogenesis and/or testicular development, were identified to be hypermethylated in male patients with CH. The hypermethylation of these sites was further validated in another 40 patients with CH and 40 matched controls with a quantitative bisulfite pyrosequencing method, and the methylation levels of these two loci demonstrated promising diagnostic capacities for CH. The present results suggested that aberrant methylation of genes may be involved in the pathogenesis of CH, and hypermethylation of LIMK2 and PIWIL2 may contribute to the infertility of male patients with CH. Further studies are required to elucidate the underlying mechanisms of the epigenetic regulation of these genes.

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