Elevated SLC26A4 gene promoter methylation is associated with the risk of presbycusis in men

Xu,Jin; Zheng,Jiachen; Shen,Wanjing; Ma,Lili; Zhao,Ming; Wang,Xubo; Tang,Jiyuan; Yan,Jihong; Wu,Zhenhua; Zou,Zuquan; Bu,Shizhong; Xi,Yang

doi:10.3892/mmr.2017.6565

Elevated SLC26A4 gene promoter methylation is associated with the risk of presbycusis in men

Authors:
- Jin Xu
- Jiachen Zheng
- Wanjing Shen
- Lili Ma
- Ming Zhao
- Xubo Wang
- Jiyuan Tang
- Jihong Yan
- Zhenhua Wu
- Zuquan Zou
- Shizhong Bu
- Yang Xi
View Affiliations

Affiliations: Department of Otorhinolaryngology, Ningbo No. 7 Hospital, Ningbo, Zhejiang 315202, P.R. China, Zhejiang Provincial Key Laboratory of Pathophysiology, Diabetes Center, Institute of Biochemistry and Molecular Biology, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211, P.R. China, Department of Otorhinolaryngology, Lihuili Hospital, Ningbo, Zhejiang 315041, P.R. China
Published online on: May 10, 2017 https://doi.org/10.3892/mmr.2017.6565
Pages: 347-352

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Presbycusis affects approximately one-third of people over the age of 65 and is a worldwide health problem. In the current study, whether the methylation level of solute carrier family 26 member 4 (SLC26A4) predicted an increased risk of presbycusis was investigated. Peripheral blood samples from 102 patients with presbycusis and 104 controls were collected, and the methylation of the CpG sites of SLC26A4 was measured by applying pyrosequencing technology combined with sodium bisulfate DNA conversion chemistry. Within the SLC26A4 promoter region, one CpG site (CpG3) exhibited a significantly (P<0.0001) greater methylation level in the patients with presbycusis (26.5±5.56%) compared with the controls (23.8±3.85%). Significantly different CpG3 methylation levels were observed between the patients with presbycusis and the controls among the male participants (P=0.0004). In addition, a significant decrease in the transcriptional level of SLC26A4 in peripheral blood was observed in the patients with presbycusis compared with the controls. Furthermore, analyses of the receiver operating characteristic (ROC) curves indicated that CpG3 methylation at the SLC26A4 promoter predicted the risk of presbycusis in the male participants (AUC=0.684, 95% CI=0.584‑0.784, P=0.001). The results demonstrated the significance of the CpG site methylation level of SLC26A4, and thus provides a potential marker for the diagnosis of presbycusis.

View Figures

View References

1	Kidd Iii AR and Bao J: Recent advances in the study of age-related hearing loss: A mini-review. Gerontology. 58:490–496. 2012. View Article : Google Scholar : PubMed/NCBI
2	Dai P, Yuan Y, Huang D, Zhu X, Yu F, Kang D, Yuan H, Wu B, Han D and Wong LJ: Molecular etiology of hearing impairment in Inner Mongolia: Mutations in SLC26A4 gene and relevant phenotype analysis. J Transl Med. 6:742008. View Article : Google Scholar : PubMed/NCBI
3	Fransen E, Lemkens N, Van Laer L and Van Camp G: Age-related hearing impairment (ARHI): Environmental risk factors and genetic prospects. Exp Gerontol. 38:353–359. 2003. View Article : Google Scholar : PubMed/NCBI
4	Ohlemiller KK: Mechanisms and genes in human strial presbycusis from animal models. Brain Res. 1277:70–83. 2009. View Article : Google Scholar : PubMed/NCBI
5	Du W, Wang Q, Zhu Y, Wang Y and Guo Y: Associations between GJB2, mitochondrial 12S rRNA, SLC26A4 mutations, and hearing loss among three ethnicities. Biomed Res Int. 2014:7468382014. View Article : Google Scholar : PubMed/NCBI
6	Yamasoba T, Lin FR, Someya S, Kashio A, Sakamoto T and Kondo K: Current concepts in age-related hearing loss: Epidemiology and mechanistic pathways. Hear Res. 303:30–38. 2013. View Article : Google Scholar : PubMed/NCBI
7	Lo Nigro C, Monteverde M, Lee S, Lattanzio L, Vivenza D, Comino A, Syed N, McHugh A, Wang H, Proby C, et al: NT5E CpG island methylation is a favourable breast cancer biomarker. Br J Cancer. 107:75–83. 2012. View Article : Google Scholar : PubMed/NCBI
8	Tang L, Ye H, Hong Q, Wang L, Wang Q, Wang H, Xu L, Bu S, Zhang L, Cheng J, et al: Elevated CpG island methylation of GCK gene predicts the risk of type 2 diabetes in Chinese males. Gene. 547:329–333. 2014. View Article : Google Scholar : PubMed/NCBI
9	Joo MK, Kim KH, Park JJ, Yoo HS, Choe J, Kim HJ, Lee BJ, Kim JS and Bak YT: CpG island promoter hypermethylation of Ras association domain family 1A gene contributes to gastric carcinogenesis. Mol Med Rep. 11:3039–3046. 2015.PubMed/NCBI
10	Yoshino T, Sato E, Nakashima T, Teranishi M, Yamamoto H, Otake H and Mizuno T: Distribution of pendrin in the organ of Corti of mice observed by electron immunomicroscopy. Eur Arch Otorhinolaryngol. 263:699–704. 2006. View Article : Google Scholar : PubMed/NCBI
11	Ledford H: Language: Disputed definitions. Nature. 455:1023–1028. 2008. View Article : Google Scholar : PubMed/NCBI
12	Luo HJ, Yang T and Wu H: Genetic research of age-related hearing impairment. Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi. 48:78–81. 2013.(In Chinese). PubMed/NCBI
13	Wangemann P, Nakaya K, Wu T, Maganti RJ, Itza EM, Sanneman JD, Harbidge DG, Billings S and Marcus DC: Loss of cochlear HCO3- secretion causes deafness via endolymphatic acidification and inhibition of Ca²⁺ reabsorption in a Pendred syndrome mouse model. Am J Physiol Renal Physiol. 292:F1345–F1353. 2007. View Article : Google Scholar : PubMed/NCBI
14	Kim HM and Wangemann P: Epithelial cell stretching and luminal acidification lead to a retarded development of stria vascularis and deafness in mice lacking pendrin. PLoS One. 6:e179492011. View Article : Google Scholar : PubMed/NCBI
15	Song H, Sun W, Ye G, Ding X, Liu Z, Zhang S, Xia T, Xiao B, Xi Y and Guo J: Long non-coding RNA expression profile in human gastric cancer and its clinical significances. J Transl Med. 11:2252013. View Article : Google Scholar : PubMed/NCBI
16	Tanaka N, Huttenhower C, Nosho K, Baba Y, Shima K, Quackenbush J, Haigis KM, Giovannucci E, Fuchs CS and Ogino S: Novel application of structural equation modeling to correlation structure analysis of CpG island methylation in colorectal cancer. Am J Pathol. 177:2731–2740. 2010. View Article : Google Scholar : PubMed/NCBI
17	Song MA, Tiirikainen M, Kwee S, Okimoto G, Yu H and Wong LL: Elucidating the landscape of aberrant DNA methylation in hepatocellular carcinoma. PLoS One. 8:e557612013. View Article : Google Scholar : PubMed/NCBI
18	Sriraksa R, Zeller C, El-Bahrawy MA, Dai W, Daduang J, Jearanaikoon P, Chau-In S, Brown R and Limpaiboon T: CpG-island methylation study of liver fluke-related cholangiocarcinoma. Br J Cancer. 104:1313–1318. 2011. View Article : Google Scholar : PubMed/NCBI
19	Khan MR, Bashir R and Naz S: SLC26A4 mutations in patients with moderate to severe hearing loss. Biochem Genet. 51:514–523. 2013. View Article : Google Scholar : PubMed/NCBI
20	Uchida Y, Sugiura S, Ando F, Nakashima T and Shimokata H: Hearing impairment risk and interaction of folate metabolism related gene polymorphisms in an aging study. BMC Med Genet. 12:352011. View Article : Google Scholar : PubMed/NCBI
21	Yang T, Vidarsson H, Rodrigo-Blomqvist S, Rosengren SS, Enerback S and Smith RJ: Transcriptional control of SLC26A4 is involved in Pendred syndrome and nonsyndromic enlargement of vestibular aqueduct (DFNB4). Am J Hum Genet. 80:1055–1063. 2007. View Article : Google Scholar : PubMed/NCBI
22	Rozenfeld J, Efrati E, Adler L, Tal O, Carrithers SL, Alper SL and Zelikovic I: Transcriptional regulation of the pendrin gene. Cell Physiol Biochem. 28:385–396. 2011. View Article : Google Scholar : PubMed/NCBI