Current issue
Archive
Manuscripts accepted
About the Journal
Editorial office
Editorial board
Abstracting and indexing
Subscription
Contact
Ethical standards and procedures
Most read articles
Instructions for authors
Article Processing Charge (APC)
Regulations of paying article processing charge (APC)
OTOLARYNGOLOGY / BASIC RESEARCH
Analysis of major otosclerosis-associated variants in RELN and TGFB1 genes in Polish patients
1
Department of Genetics, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland
2
Postgraduate School of Molecular Medicine, Medical University of Warsaw, Warsaw, Poland
3
Oto-Rhino-Laryngology Surgery Clinic, Institute of Physiology and Pathology of Hearing, Warsaw/Kajetany, Poland
Submission date: 2019-08-16
Final revision date: 2019-12-23
Acceptance date: 2019-12-26
Online publication date: 2020-09-16
Publication date: 2024-07-24
Arch Med Sci 2024;20(3):962-966
KEYWORDS
TOPICS
ABSTRACT
Introduction:
Otosclerosis (OTSC) is one of the most common causes of progressive adult-onset hearing loss in the Caucasian population, with a female preponderance. The etiology of OTSC is complex and there are a number of genetic variants reported to be associated with OTSC susceptibility, but no data on the genetic background of OTSC in patients originating from the central-eastern part of Europe have been available. The purpose of our study was to investigate in Polish patients the frequency of genetic variants previously reported to be most strongly associated with OTSC.
Material and methods:
Genomic DNA was isolated from blood samples or buccal swabs. Variants in TGFB1 (rs1800472) and RELN (rs39335, rs39350, rs39374) were genotyped in surgically confirmed OTSC patients (n = 94) and a control group (n = 198) using custom TaqMan SNP genotyping assays and real-time PCR. Allele and genotype frequencies were compared between the groups in statistical analysis and the odds ratios with 95% confidence intervals were calculated to estimate the risk.
Results:
For all of the tested variants the distributions of alleles and genotypes were not statistically significantly different between OTCS patients and the control group. There were also no statistically significant differences in relation to gender of the tested subjects.
Conclusions:
Despite multiple confirmatory studies on TGFB1 and RELN association with OTSC development in some populations, no significant association between the studied variants and OTSC was found in Polish patients. Our results indicate the presence of inter-population differences in OTSC susceptibility factors and confirm the large genetic heterogeneity of this disorder.
Otosclerosis (OTSC) is one of the most common causes of progressive adult-onset hearing loss in the Caucasian population, with a female preponderance. The etiology of OTSC is complex and there are a number of genetic variants reported to be associated with OTSC susceptibility, but no data on the genetic background of OTSC in patients originating from the central-eastern part of Europe have been available. The purpose of our study was to investigate in Polish patients the frequency of genetic variants previously reported to be most strongly associated with OTSC.
Material and methods:
Genomic DNA was isolated from blood samples or buccal swabs. Variants in TGFB1 (rs1800472) and RELN (rs39335, rs39350, rs39374) were genotyped in surgically confirmed OTSC patients (n = 94) and a control group (n = 198) using custom TaqMan SNP genotyping assays and real-time PCR. Allele and genotype frequencies were compared between the groups in statistical analysis and the odds ratios with 95% confidence intervals were calculated to estimate the risk.
Results:
For all of the tested variants the distributions of alleles and genotypes were not statistically significantly different between OTCS patients and the control group. There were also no statistically significant differences in relation to gender of the tested subjects.
Conclusions:
Despite multiple confirmatory studies on TGFB1 and RELN association with OTSC development in some populations, no significant association between the studied variants and OTSC was found in Polish patients. Our results indicate the presence of inter-population differences in OTSC susceptibility factors and confirm the large genetic heterogeneity of this disorder.
REFERENCES (23)
1.
Babcock TA, Liu XZ. Otosclerosis: from genetics to molecular biology. Otolaryngol Clin North Am 2018; 51: 305-18.
2.
Crompton M, Cadge BA, Ziff JL, et al. The epidemiology of otosclerosis in a British cohort. Otol Neurotol 2019; 40: 22-30.
3.
Declau F, Van Spaendonck M, Timmermans JP, et al. Prevalence of otosclerosis in an unselected series of temporal bones. Otol Neurotol 2001; 22: 596-602.
5.
Schrauwen I, Khalfallah A, Ealy M, et al. COL1A1 association and otosclerosis: a meta-analysis. Am J Med Genet A 2012; 158A: 1066-70.
6.
Imauchi Y, Jeunemaitre X, Boussion M, Ferrary E, Sterkers O, Grayeli AB. Relation between renin-angiotensin- aldosterone system and otosclerosis: a genetic association and in vitro study. Otol Neurotol 2008; 29: 295-301.
7.
Schrauwen I, Thys M, Vanderstraeten K, et al. Association of bone morphogenetic proteins with otosclerosis. J Bone Miner Res 2008; 23: 507-16.
8.
Mowat AJ, Crompton M, Ziff JL, et al. Evidence of distinct RELN and TGFB1 genetic associations in familial and non-familial otosclerosis in a British population. Hum Genet 2018; 137: 357-63.
9.
Ertugay OC, Ata P, Kalaycik Ertugay C, Kaya KS, Tatlipinar A, Kulekci S. Association of COL1A1 polymorphism in Turkish patients with otosclerosis. Am J Otolaryngol 2013; 34: 403-6.
10.
Sommen M, Van Camp G, Liktor B, et al. Genetic association analysis in a clinically and histologically confirmed otosclerosis population confirms association with the TGFB1 gene but suggests an association of the RELN gene with a clinically indistinguishable otosclerosis-like phenotype. Otol Neurotol 2014; 35: 1058-64.
11.
Priyadarshi S, Ray CS, Panda KC, et al. Genetic association and gene expression profiles of TGFB1 and the contribution of TGFB1 to otosclerosis susceptibility. J Bone Miner Res 2013; 28: 2490-7.
12.
Schrauwen I, Ealy M, Huentelman MJ, et al. A genome- wide analysis identifies genetic variants in the RELN gene associated with otosclerosis. Am J Hum Genet 2009; 84: 328-38.
13.
Schrauwen I, Ealy M, Fransen E, et al. Genetic variants in the RELN gene are associated with otosclerosis in multiple European populations. Hum Genet 2010; 127: 155-62.
14.
Khalfallah A, Schrauwen I, Mnaja M, et al. Genetic variants in RELN are associated with otosclerosis in a non-European population from Tunisia. Ann Hum Genet 2010; 74: 399-405.
15.
Zara-Lopes T, Galbiatti-Dias ALS, Castanhole-Nunes MMU, et al. Polymorphisms in MTHFR, MTR, RFC1 and CssS genes involved in folate metabolism and thyroid cancer: a case-control study. Arch Med Sci 2019; 15: 522-30.
16.
Zemtsovskaja G, Abina J, Meigas K, Pilt K, Viigimaa M. Pulse wave velocity and its gender-related associations with cardiovascular risk factors in a high cardiovascular risk population. Arch Med Sci Atheroscler Dis 2018; 3: e99-e105.
17.
Barrett JC. Haploview: visualization and analysis of SNP genotype data. Cold Spring Harb Protoc 2009; 2009: pdbip71.
18.
Alyousef YM, Borgio JF, AbdulAzeez S, et al. Association of MBL2 gene polymorphism with dental caries in Saudi children. Caries Res 2017; 51: 12-6.
19.
Thys M, Schrauwen I, Vanderstraeten K, et al. Detection of rare nonsynonymous variants in TGFB1 in otosclerosis patients. Ann Hum Genet 2009; 73: 171-5.
20.
Khalfallah A, Schrauwen I, Mnejja M, et al. Association of COL1A1 and TGFB1 polymorphisms with otosclerosis in a Tunisian population. Ann Hum Genet 2011; 75: 598-604.
21.
Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of Hardy-Weinberg equilibrium. Am J Hum Genet 2005; 76: 887-93.
22.
Belohlavkova P, Vrbacky F, Voglova J, et al. The significance of enzyme and transporter polymorphisms for imatinib plasma levels and achieving an optimal response in chronic myeloid leukemia patients. Arch Med Sci 2018; 14: 1416-23.
23.
Sadaf T, John P, Bhatti A, Malik JM. Lack of association of -863C/A (rs1800630) polymorphism of tumor necrosis factor-a gene with rheumatoid arthritis. Arch Med Sci 2019; 15: 531-6.
Share
RELATED ARTICLE
| eISSN: | 1896-9151 |
| ISSN: | 1734-1922 |
We process personal data collected when visiting the website. The function of obtaining information about users and their behavior is carried out by voluntarily entered information in forms and saving cookies in end devices. Data, including cookies, are used to provide services, improve the user experience and to analyze the traffic in accordance with the Privacy policy. Data are also collected and processed by Google Analytics tool (more).
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
You can change cookies settings in your browser. Restricted use of cookies in the browser configuration may affect some functionalities of the website.
