Polymorphism of the Serotonin Transporter Gene and the Peripheral 5-Hydroxytryptamine in Obstructive Sleep Apnea: What Do We Know and What are We Looking for? A Systematic Review of the Literature.
5-HTTLPR
5-HTTVNTR
obesity
sleep disorder breathing
Journal
Nature and science of sleep
ISSN: 1179-1608
Titre abrégé: Nat Sci Sleep
Pays: New Zealand
ID NLM: 101537767
Informations de publication
Date de publication:
2021
2021
Historique:
received:
21
08
2020
accepted:
18
12
2020
entrez:
19
2
2021
pubmed:
20
2
2021
medline:
20
2
2021
Statut:
epublish
Résumé
Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA. To examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity. A systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case-control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep. The inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added - English articles published in the last 15 years. Studies that were not included were reviews and case reports. In order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list. The search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT) - variable number of tandem repeats (VNTR) and linked polymorphic region (LPR) - are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long (L/L) allele genotype were associated with a higher prevalence of OSA and the L allele with a higher apnea-hypopnea index and a longer time during sleep with oxygen desaturation. The main limitation of the present study consists of heterogeneity of the information. Being a less studied subject, randomized trials are not widely available and most data were obtained from case-control trials. Moreover, the included material indirectly approached the subject by demonstrating the effects of serotoninergic system over the metabolism, the connection between serotonin and obesity, factors which are implied in the pathogenesis of OSA. The two polymorphisms of serotonin gene can be considered important factors in the diagnosis and management of OSA.
Sections du résumé
BACKGROUND
BACKGROUND
Obstructive sleep apnea (OSA) is a highly prevalent disease with substantial public health burden. In most of the cases, there is a genetic predisposition to OSA. Serotonin/T-HydroxyTriptamine (5-HT) plays a key role in ventilatory stimulation, while the polymorphism of the serotonin transporter gene (STG) leads to alterations in serotonin level, making it important in OSA.
OBJECTIVE
OBJECTIVE
To examine whether the 5-HydroxyTriptamine and the genetic predisposition influence the incidence and evolution of OSA, we reviewed randomized, controlled trials and observational studies on the selected topic. The secondary objective was to determine the metabolic effects of the circulating serotonin in other tissues (liver, pancreas, gut, brown adipose tissue, and white adipose tissue) and its role in the development of obesity.
DATA SOURCES
METHODS
A systematic review of English articles was performed based on PubMed and the Cochrane Library databases. Search filters included randomized controlled trial, controlled clinical trial, random allocation, double-blind method, and case-control studies and used the following keywords: Brain Serotonin OR Serotonin Transporter Gene Polymorphism OR Peripheral 5-HydroxyTryptamine AND Obstructive Sleep Apnea OR Sleep Disorder Breathing OR brain serotonin AND OSA OR serotonin transporter gene OR Peripheral 5-Hydroxytryptamine AND Sleep.
STUDY ELIGIBILITY CRITERIA
METHODS
The inclusion criteria for the current review were previous diagnosis of OSA, age above 18 years, and articles including quantitative data about serotonin transporter gene or peripheral serotonin. Language and time criteria were added - English articles published in the last 15 years. Studies that were not included were reviews and case reports.
STUDY APPRAISAL AND SYNTHESIS METHODS
METHODS
In order to study the serotonin function, a literature research was conducted in the databases Pubmed and Cochrane Library. The following search terms were used: serotonin, 5-hydroxytryptamine, serotonin transporter gene. A critical appraisal of the included studies was performed with the Newcastle-Ottawa scale (NOS) and Delphi list.
RESULTS
RESULTS
The search yielded 1210 articles, from which 43 were included. The included studies suggest that the two polymorphisms of serotonin transporter gene (5HTT) - variable number of tandem repeats (VNTR) and linked polymorphic region (LPR) - are strong candidates in the pathogenesis of OSA. The allele 10 of 5HTTVNTR and the long/long (L/L) allele genotype were associated with a higher prevalence of OSA and the L allele with a higher apnea-hypopnea index and a longer time during sleep with oxygen desaturation.
LIMITATIONS
CONCLUSIONS
The main limitation of the present study consists of heterogeneity of the information. Being a less studied subject, randomized trials are not widely available and most data were obtained from case-control trials. Moreover, the included material indirectly approached the subject by demonstrating the effects of serotoninergic system over the metabolism, the connection between serotonin and obesity, factors which are implied in the pathogenesis of OSA.
CONCLUSION AND IMPLICATIONS OF KEY FINDINGS
CONCLUSIONS
The two polymorphisms of serotonin gene can be considered important factors in the diagnosis and management of OSA.
Identifiants
pubmed: 33603523
doi: 10.2147/NSS.S278170
pii: 278170
pmc: PMC7881775
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
125-139Informations de copyright
© 2021 Maierean et al.
Déclaration de conflit d'intérêts
The authors report no conflicts of interest in this work.
Références
Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2005 Oct;22(5):533-6
pubmed: 16215942
J Clin Psychiatry. 2003 Oct;64(10):1195-200; quiz, 1274-6
pubmed: 14658968
Pharmacogenomics. 2010 Jun;11(6):773-80
pubmed: 20504252
J Thorac Dis. 2015 May;7(5):920-9
pubmed: 26101650
Diabetes. 2010 Jun;59(6):1302-11
pubmed: 20185816
Nat Med. 2010 Jul;16(7):804-8
pubmed: 20581837
JAMA. 2000 Dec 20;284(23):3015-21
pubmed: 11122588
Laryngoscope. 2005 May;115(5):832-6
pubmed: 15867649
J Cereb Blood Flow Metab. 1997 Aug;17(8):833-45
pubmed: 9290581
Chest. 1999 May;115(5):1397-401
pubmed: 10334159
Am J Respir Crit Care Med. 1996 Feb;153(2):776-86
pubmed: 8564132
Physiol Behav. 2008 Mar 18;93(4-5):724-32
pubmed: 18177905
Psychosom Med. 2007 Sep-Oct;69(7):621-4
pubmed: 17766685
Sleep. 2008 Nov;31(11):1535-41
pubmed: 19014073
Int J Obes (Lond). 2014 May;38(5):724-9
pubmed: 23900445
J Neural Transm Gen Sect. 1994;95(2):157-62
pubmed: 7865169
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19420-5
pubmed: 24218571
Sci Rep. 2017 Mar 10;7:44392
pubmed: 28281681
Sleep. 2010 Mar;33(3):343-7
pubmed: 20337192
Ann N Y Acad Sci. 2002 Jun;967:571-5
pubmed: 12079891
Clinics (Sao Paulo). 2014 Nov;69(11):710-3
pubmed: 25518026
N Engl J Med. 1993 Apr 29;328(17):1230-5
pubmed: 8464434
J Clin Sleep Med. 2012 Oct 15;8(5):597-619
pubmed: 23066376
Endocrinology. 2010 Oct;151(10):4776-86
pubmed: 20685881
Nat Med. 2015 Feb;21(2):166-72
pubmed: 25485911
Brain Res. 2006 Apr 26;1085(1):11-8
pubmed: 16581041
Clin Endocrinol (Oxf). 2018 Apr;88(4):549-555
pubmed: 29292526
Am J Respir Crit Care Med. 2006 Nov 15;174(10):1139-44
pubmed: 16888290
Curr Neuropharmacol. 2008 Dec;6(4):367-78
pubmed: 19587857
Am J Respir Crit Care Med. 2001 Apr;163(5):1191-7
pubmed: 11316658
Endocrinology. 2008 Apr;149(4):1773-85
pubmed: 18162515
Sleep. 2007 Dec;30(12):1667-73
pubmed: 18246976
Am J Hum Genet. 2005 Jan;76(1):100-11
pubmed: 15558495
J Clin Epidemiol. 1998 Dec;51(12):1235-41
pubmed: 10086815
J Clin Sleep Med. 2017 Mar 15;13(3):479-504
pubmed: 28162150
Physiol Rev. 2010 Jan;90(1):47-112
pubmed: 20086074
Nat Sci Sleep. 2018 Sep 04;10:255-269
pubmed: 30214331
Biol Psychiatry. 1998 Aug 1;44(3):151-62
pubmed: 9693387
Pediatr Pulmonol. 2002 Sep;34(3):209-17
pubmed: 12203850
Nat Neurosci. 2006 Feb;9(2):227-33
pubmed: 16415870
Am J Respir Crit Care Med. 2002 May 1;165(9):1217-39
pubmed: 11991871
J Neurosci. 2015 Apr 8;35(14):5884-9
pubmed: 25855196
Multidiscip Respir Med. 2019 Feb 14;14:8
pubmed: 30809382
Int J Geriatr Psychiatry. 2014 Mar;29(3):227-35
pubmed: 23754303
Liver Int. 2013 Apr;33(4):535-43
pubmed: 23362947
Diabetes Res Clin Pract. 2002 Nov;58(2):123-9
pubmed: 12213354
J Exp Biol. 1988 Jul;137:513-27
pubmed: 3209972
Sleep. 2007 Aug;30(8):1049-53
pubmed: 17702275
J Neurosci. 2005 Dec 7;25(49):11231-8
pubmed: 16339018
Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16354-9
pubmed: 20805497
Eur Respir J. 2008 Nov;32(5):1304-8
pubmed: 18579548
J Clin Epidemiol. 2009 Oct;62(10):e1-34
pubmed: 19631507
Diabetes. 2011 Dec;60(12):3208-16
pubmed: 22013016
J Prosthodont. 2019 Feb;28(2):e843-e848
pubmed: 28834052
Science. 2006 Apr 7;312(5770):104-7
pubmed: 16601191
Mol Psychiatry. 1997 Oct-Nov;2(6):457-62
pubmed: 9399688
PLoS Biol. 2009 Oct;7(10):e1000229
pubmed: 19859528
Diabetes Care. 2012 Jan;35(1):163-7
pubmed: 22100965
Auton Neurosci. 2010 Feb 16;153(1-2):47-57
pubmed: 19729349
JAMA. 2004 Apr 28;291(16):2013-6
pubmed: 15113821
Am J Respir Crit Care Med. 1995 Mar;151(3 Pt 1):682-7
pubmed: 7881656
Otolaryngol Clin North Am. 2018 Aug;51(4):827-833
pubmed: 29779616
Cell Rep. 2016 Dec 20;17(12):3281-3291
pubmed: 28009296
Anesth Analg. 2017 Jan;124(1):179-191
pubmed: 27861433
PLoS One. 2013;8(3):e58717
pubmed: 23554917
J Neurophysiol. 2015 Jul;114(1):233-43
pubmed: 25925320
Obesity (Silver Spring). 2012 Jan;20(1):233-8
pubmed: 21836641
Curr Genomics. 2009 Apr;10(2):119-26
pubmed: 19794884
Sleep Breath. 2013 Dec;17(4):1241-8
pubmed: 23494654
Nat Commun. 2015 Apr 13;6:6794
pubmed: 25864946
Neuropsychiatr Dis Treat. 2006 Sep;2(3):309-26
pubmed: 19412478
Diabetologia. 2016 Apr;59(4):744-54
pubmed: 26733006
Nutr Healthy Aging. 2019 Dec 19;5(3):167-184
pubmed: 31984245
Chest. 1995 Jun;107(6):1545-51
pubmed: 7781344
Lancet Respir Med. 2015 Apr;3(4):310-8
pubmed: 25682233
J Clin Psychiatry. 1984 Jul;45(7):287-90
pubmed: 6735987
Medicine (Baltimore). 2016 Sep;95(37):e4833
pubmed: 27631236
Sleep. 1991 Dec;14(6):486-95
pubmed: 1798880
Neuron. 2011 Feb 24;69(4):664-79
pubmed: 21338878
Arch Intern Med. 2006 Sep 18;166(16):1768-74
pubmed: 16983057
Obesity (Silver Spring). 2010 Jul;18(7):1369-77
pubmed: 19876004
Metab Syndr Relat Disord. 2007 Dec;5(4):323-30
pubmed: 18370802