METTL14 gene polymorphisms influence hepatoblastoma predisposition in Chinese children: Evidences from a seven-center case-control study

Huitong Chen; Zhen Chen; Mi Wang; Jiao Zhang; Yong Li; Li Li; Suhong Li; Jiwen Cheng; Xianqiang Wang; Huimin Xia; Zhonghua Yang; Jing He

doi:10.1016/j.gene.2021.146050

METTL14 gene polymorphisms influence hepatoblastoma predisposition in Chinese children: Evidences from a seven-center case-control study

Gene. 2022 Jan 30:809:146050. doi: 10.1016/j.gene.2021.146050. Epub 2021 Oct 29.

Authors

Huitong Chen¹, Zhen Chen², Mi Wang¹, Jiao Zhang³, Yong Li⁴, Li Li⁵, Suhong Li⁶, Jiwen Cheng⁷, Xianqiang Wang⁸, Huimin Xia¹, Zhonghua Yang⁹, Jing He¹⁰

Affiliations

¹ Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China.
² Department of Pediatric Surgery, Capital Institute of Pediatrics, Beijing 100020, Beijing, China.
³ Department of Pediatric Surgery, the First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, China.
⁴ Department of Pediatric Surgery, Hunan Children's Hospital, Changsha 410004, Hunan, China.
⁵ Kunming Key Laboratory of Children Infection and Immunity, Yunnan Key Laboratory of Children's Major Disease Research, Yunnan Institute of Pediatrics Research, Yunnan Medical Center for Pediatric Diseases, Kunming Children's Hospital, Kunming 650228, Yunnan, China.
⁶ Department of Pathology, Children Hospital and Women Health Center of Shanxi, Taiyuan 030013, Shanxi, China.
⁷ Department of Pediatric Surgery, the Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, Shaanxi, China.
⁸ Department of General Pediatrics, Senior Department of Pediatrics, National Engineering Laboratory for Birth Defects Prevention and Control of Key Technology, Beijing Key Laboratory of Pediatric Organ Failure, the Seventh Medical Center of PLA General Hospital, Beijing 100000, China.
⁹ Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang 110004, Liaoning, China. Electronic address: yangzh5283@163.com.
¹⁰ Department of Pediatric Surgery, Guangzhou Institute of Pediatrics, Guangdong Provincial Key Laboratory of Research in Structural Birth Defect Disease, Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou 510623, Guangdong, China. Electronic address: hejing@gwcmc.org.

PMID: 34743822
DOI: 10.1016/j.gene.2021.146050

Abstract

Hepatoblastoma as the most prevalent hepatic malignancy in children, its etiology remains unclear. N⁶-Methyladenosine (m⁶A) modification which can modify various physiological processes, plays a critical role in tumorigenesis. Methyltransferase-like 14 (METTL14), an important component of the m⁶A methyltransferase complex, remains elusive during hepatoblastoma occurrence and development. We explored the relationship between METTL14 gene polymorphisms (rs1064034 T > A, rs298982 G > A, rs62328061 A > G, rs9884978 G > A, and rs4834698 T > C) and hepatoblastoma susceptibility from 313 patients and 1446 controls. The role of METTL14 polymorphisms in hepatoblastoma was evaluated by odds ratios (ORs) and 95% confidence intervals (CIs). Of the included subjects, 308 patients and 1444 controls were successfully genotyped. We did not find any significant correlation between the risk of hepatoblastoma and the five potentially functional METTL14 polymorphisms individually. However, the presence of 4-5 risk genotypes exhibited a significant increased hepatoblastoma risk (adjusted OR = 1.32, 95% CI = 1.03-1.69, P = 0.031) compared to those carriers with 0-3 risk genotypes. Furthermore, the stratified analysis demonstrated that the rs1064034 AA genotype, rs62328061 AG/GG genotypes, rs4834698 TC/CC genotypes, and 4-5 risk genotypes were related to hepatoblastoma susceptibility in certain subgroups. The expression quantitative trait loci (eQTL) analysis revealed that rs1064034 T > A and rs4834698 T > C were correlated with the expression levels of METTL14 and its surrounding genes. Prospectively, these findings suggested that METTL14 polymorphisms may correlation with hepatoblastoma susceptibility and provide a fresh insight into the genetic underpinnings of m⁶A modification in hepatoblastoma.

Keywords: Hepatoblastoma; M(6)A; METTL14; Polymorphism; Susceptibility.

Publication types

Multicenter Study

MeSH terms

Case-Control Studies
Child, Preschool
Female
Genetic Predisposition to Disease
Hepatoblastoma / genetics*
Humans
Infant
Liver Neoplasms / genetics*
Male
Methyltransferases / genetics*
Polymorphism, Single Nucleotide*
Quantitative Trait Loci

Substances

METTL14 protein, human
Methyltransferases