Abstract
Charcot–Marie–Tooth disease type 1A (CMT1A) is caused by 1.5-fold increased dosage of the PMP22; however, onset age and severity vary considerably among patients. The exact reason behind these phenotypic heterogeneities has rarely been discovered yet. Because miRNAs are the key regulators of gene expression, we speculated that variants of miRNAs might be the genetic modifiers for CMT1A. This study noticed a common single nucleotide polymorphism (n.86T > C, rs2292832) in the miR-149 which was predicted to target several CMT causing genes including PMP22. The rs2292832 was located near the 3′ end of the precursor microRNA of the miR-149. We performed an association study between the rs2292832 polymorphism and clinical phenotypes of CMT1A in subjects consisting of 176 unrelated Korean CMT1A patients and 176 controls. From this study, we observed that rs2292832 was closely associated to the onset age and severity of CMT1A. Particularly, the TC and CC genotypes were significantly associated with late onset and mild symptom. Therefore, we suggest that the rs2292832 variant in the miR-149 is a potential candidate as a genetic modifier which affects the phenotypic heterogeneity of CMT1A. This study may provide the first evidence that polymorphism in the miR gene is associated with the CMT1A phenotype.
Original language | English |
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Pages (from-to) | 502-507 |
Number of pages | 6 |
Journal | Neuromuscular Disorders |
Volume | 28 |
Issue number | 6 |
DOIs | |
State | Published - Jun 2018 |
Bibliographical note
Funding Information:The authors would like to thank all the participants and their families. This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare ( HI14C3484 and HI15C1560 ), and the National Research Foundation funded by the MSIP ( 2017R1A2A2A05001356 and 2017R1A2B2004699 ), Republic of Korea.
Funding Information:
The authors would like to thank all the participants and their families. This study was supported by the Korean Health Technology R&D Project, Ministry of Health & Welfare (HI14C3484 and HI15C1560), and the National Research Foundation funded by the MSIP (2017R1A2A2A05001356 and 2017R1A2B2004699), Republic of Korea.
Publisher Copyright:
© 2018 Elsevier B.V.
Keywords
- Association study
- CMT1A
- Genetic modifier
- miR-149
- Phenotypic heterogeneity