Journal of Otology & RhinologyISSN: 2324-8785

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Review Article, J Otol Rhinol Vol: 4 Issue: 3

Genetic Factors in Vestibular Function and Motion Sickness

Glenn W Knox*
Department of Surgery, Division of Otolaryngology, University of Florida Health-Jacksonville, Jacksonville, FL 32209, USA
Corresponding author : Glenn W Knox
Associate Professor, Department of Surgery, Division of Otolaryngology, University of Florida Health-Jacksonville, Jacksonville, FL 32209, USA
Tel: (904) 383-1017; Fax: (904) 244-2638
E-mail: [email protected]
Received: October 20, 2014 Accepted: January 27, 2015 Published: April 28, 2015
Citation: Knox G (2015) Genetic Factors in Vestibular Function and Motion Sickness. J Otol Rhinol 4:3. doi:10.4172/2324-8785.1000225

Abstract

Genetic Factors in Vestibular Function and Motion Sickness

Objectives: To determine if motion sickness has a genetic basis, and, if so, to determine if there is a correlation between motion sickness genetic factors and genetic factors governing vestibular function.

Data sources: The scope of review in this paper includes studies involving collection of primary data on susceptibility to motion sickness, correlated with any genetic factor; and, review articles concerning vestibular function and genetic factors.

Study selection: A literature review was conducted to obtain articles that pertained to genetic factors governing vestibular function. To locate articles, sources including PubMed were utilized to locate review articles with the key words genetic,vestibular and motion sickness.

Data extraction: Requirement that articles are written in English and published in the past 25 years.

Data synthesis: Direct correlation.

Conclusions: The selected articles revealed that: (1) Genetic polymorphism of the alpha-2a adrenergic receptor is correlated with motion sickness susceptibility in that the 6.3 Kb gene is correlated with increased susceptibility to motion sickness as compared to the 6.7 Kb polymorph; and (2) There is a lack of significant genetic correlation between the gene for the alpha-2a adrenergic receptor and genetic factors governing vestibular function. This data is in agreement with the observation that individuals who are highly susceptible to motion sickness tend to have normal vestibular function. In other words, subjects with a lack of peripheral vestibular function are generally resistant to motion sickness.

Keywords: Genetic Factors; Vestibular Function; Motion Sickness

Keywords

Genetic Factors; Vestibular Function; Motion Sickness

Introduction

In a previous study by our group [1], a review of the literature suggested a hereditary factor or factors involved in motion sickness susceptibility. In particular, Lockette et al. [2] demonstrated that motion sickness susceptibility correlates with the genotype of the alpha-2a adrenergic receptor on Chromosome 10, located more specifically at 10q25.2. This gene can be the 6.3 Kb size or the 6.7 Kb size. Susceptibility to motion sickness is decreased in individuals with the 6.7 Kb gene [2]. Interestingly, Liu’s group found that the 6.3 Kb genes are 5.8 times as prevalent in Chinese individuals than non- Chinese individuals [3]. This can explain Stern’s finding that Chinese individuals typically display hypersusceptibility to motion sickness [4].
Other genetic factors are merely suggested by our literature review [1]. These include the following loci: Chromosome 6q14-15, Chromosome 1p, Chromosome 7q, and Chromosome 5p15 [1].
Therefore, we undertook another retrospective literature review to determine if there is a correlation between motion sickness genetic factors and genetic factors governing vestibular function.

Materials and Methods

A literature review was conducted to obtain articles that pertained to genetic factors governing vestibular function. To locate articles, sources including PubMed were utilized to locate review articles with the key words genetic, vestibular and motion sickness with the criteria that the article was written in English and published in the past 25 years.

Literature Review

Eppsteiner and Smith’s review [5] of genetic disorders of the vestibular system focused on peripheral vestibular disorders. These included Meniere’s disease, DFNA9, the Usher syndromes, and others. Meniere’s syndrome has been linked in a large Swedish family to chromosome 12p12.3 [5,6]. There is also evidence from analysis of a large Chilean family for a Meniere’s disease locus on 1q32.1-1q32.3 [5,7].
DFNA9 is a type of autosomal dominant nonsyndromic hearing loss with COCH being the causative gene [5]. COCH is located on chromosome 14 (14q11.2-q13). DFNA9 is similar in some respects to Meniere’s disease; however the hearing loss is early-onset and high frequency sensorineural [5]. Also, no relationship between COCH and Meniere’s disease has ever been demonstrated [5,8-10].
The Usher syndromes are autosomal recessive disorders characterized by congenital hearing loss, retinitis pigmentosa and vestibular dysfunction [5]. The Usher syndrome types associated with vestibulopathy,and their respective genes are listed in Table 1 [5,11,12]. The vestibulopathy which can typically be associated with the various Usher syndromes typically consists of caloric hypofunction or vestibular areflexia (absent caloric function) [5]. As can be seen from the table, USH1D and USH1F as well as the modifier gene are located on chromosome 10. The implications of this will be discussed below.
Table 1: Molecular classification of Usher syndrome.
Mutations in genes at the DFNB1 locus (located on chromomsome 13 at 13q11-q12), GJB2 and GJB6 are associated with autosomal recessive hearing loss [5]. It has been shown that DFNB1-associated hearing loss is sometimes associated with vestibular dysfunction [13].
Jen [14] reviewed episodic ataxia, benign recurrent vertigo including migraine-associated vertigo, bilateral vestibulopathy, and Meniere’s disease.
Familial episodic ataxias are autosomal dominant disorders [14]. These disorders are summarized in Table 2 [14,15]. As can be seen, none of the known loci are associated with chromosome 10.
Table 2: Genetic features of familial episodic ataxia syndromes.
Familial benign recurrent vertigo may be linked to 22q12 [14,16]. A related disorder, migraine associated vertigo, has been linked to polymorphism of the progesterone receptor gene (pgr) (11q22-23) [14].
Familial vertigo with bilateral vestibulopathy has not been associated with an identifiable locus [14]. This is also true for familial migraine with episodic vertigo and essential tremor [14].

Discussion

The location of the gene coding for the alpha-2a adrenergic receptor, location on chromosome 10 at 10q25.2, appears to lack widespread, significant linkage to genes mediating abnormal vestibular function. The only exceptions to this observation are the Usher syndrome genes located at 10q22.1 (cahedrin 23 cell adhesion protein), 10q21-22 (protocahedrin 15 cell adhesion protein) and the modifier gene 10q24.31 (scaffold protein) (Table 1). Abnormalities in the cell adhesion proteins and/or scaffold proteins contribute to abnormalities in the development and stability of the retina, leading to retinitis pigmentosa [17]. The Usher syndromes are extremely rare, occurring in one in 23,000 individuals in the United States [18]. Mutations in the Usher syndrome genes found on chromosome 10 would result in retinitis pigmentosa as well as vestibular dysfunction. None of the patients in Lockette’s research [2] had Usher syndrome. Perhaps the rare individuals with Usher syndrome are resistant to motion sickness but this would obviously be difficult to demonstrate, due to the rarity of this disease.*
At first glance, it may seem surprising that there is not a significant correlation between motion sickness susceptibility and hereditary vestibular dysfunction. However, there is ample evidence that the development of motion sickness depends on adequate peripheral vestibular function. For example, patients who have absent vestibular function are essentially immune to seasickness [19]. This has been noted since the late 19th century [20].
Conversely, Buyuklu’s group, for example, noted that individuals susceptible to motion sickness had normal caloric function and normal VEMPs [20]. Cohen et al. note that in regard to motion sickness, “… vestibular processing is critical to its production” [21].
The alpha-2a adrenergic receptor phenotype is strongly correlated with motion sickness [2]. This receptor mediates central and peripheral autonomic responses to stress, such as tachycardia, sweating, and nausea [2]. These responses, in a sense, are “downstream” from peripheral vestibular inputs. One interpretation of these findings is that a normal, intact peripheral vestibular system is needed to sense the sensory conflict that is expressed in autonomic functioning. Individuals who are highly susceptible to motion sickness tend to have normal peripheral vestibular systems, the better to sense noxious motion stimuli. These noxious inputs are then abnormally processed by the central and peripheral autonomic nervous system producing the symptoms of motion sickness.

Conclusion

The selected articles revealed that genetic polymorphism of the alpha-2a adrenergic receptor is correlated with motion sickness susceptibility in that the 6.3 Kb gene is correlated with increased susceptibility to motion sickness as compared to the 6.7 Kb polymorph. There is a lack of significant genetic correlation between the gene for the alpha-2a adrenergic receptor and genetic factors governing vestibular function. This is in agreement with the observation that individuals who are highly susceptible to motion sickness tend to have normal vestibular function. In other words, subjects with a lack of peripheral vestibular function are generally resistant to motion sickness.
*Our initial literature review found that a linkage of chromosome 5p15 to motion sickness was merely suggested [1]. Episodic ataxia type 6 is linked to chromosome 5p13 (Table 2). The significance of this is questionable at best.

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