Association of the –1438G/A Polymorphism of the 5-HT_2AReceptor Gene with Obstructive Sleep Apnea Syndrome

Abstract

Objective: Serotonergic neurons innervating motoneurons increase their firing rates in response to respiratory challenges, and long-term facilitation of respiratory activity in response to hypoxia is serotonin (5-HT) dependent. Polymorphism of the genes which code for 5-HT receptors may affect functions of the serotonergic system, and may be associated with obstructive sleep apnea syndrome (OSAS). The objective in this study was to assess the significance of T102C and –1438G/A polymorphisms of the 5-HT_2A receptor gene in OSAS. Methods: Fifty-five patients with OSAS and 102 healthy volun teers were included for genetic analyses of T102C and –1438G/A polymorphisms of the 5-HT_2A receptor gene. Results: For the T102C polymorphism, there was no significant difference between the patients and controls and both genders (p > 0.05). For the –1438G/A polymorphism, the A/A and G/A genotypes were overrepresented in the patients and controls, respectively (p = 0.045). In the control group, the genotypes of both genders were not significantly different (p > 0.05). In the patients, the A/A and G/A genotypes were overrepresented in males and females, respectively (p = 0.035). Concerning males, the A/A genotype was overrepresented in patients (p = 0.007). Conclusion: Serotonergic mechanisms appear to be related to OSAS. The T102C polymorphism of the 5-HT_2A receptor gene is not associated with OSAS. However, the –1438G/A polymorphism is associated with OSAS occurrence, especially in male patients. This polymorphism may also be associated with different OSAS incidences of both genders.

Polymorphisms in the 5-HTR2A gene related to obstructive sleep apnea syndrome

“…8,9,13,14 The genotype AA was significantly higher in index cases, whereas the genotypes GG/GA were higher in controls, meaning that relative to the -1438G/A polymorphism, the genotype AA may be associated with OSAS in the study population; this finding concurs with other published results. 8,9 There was a significant gender difference between index cases and controls in relation to the -1438G/A polymorphism genotypes, which was not the case with T102C polymorphism genotypes. The comparison of genotypes with gender was done because of a higher prevalence of OSAS in males, as shown in the literature.…”

“…8,9 Although the 5-HT2A receptor is mostly related with serotonin (5-HT) excitation within the representative motor nucleus of upper airways, lack of common polymorphisms or epigenetic changes that alter messenger RNA levels for the 5-HTR2A gene may explain the absence of association between the T102C polymorphism and OSAS in this population; it is also considered a silent polymorphism and was present in a similar proportion in the control group. 8,9,13,14 The genotype AA was significantly higher in index cases, whereas the genotypes GG/GA were higher in controls, meaning that relative to the -1438G/A polymorphism, the genotype AA may be associated with OSAS in the study population; this finding concurs with other published results. 8,9 There was a significant gender difference between index cases and controls in relation to the -1438G/A polymorphism genotypes, which was not the case with T102C polymorphism genotypes.…”

“…In this reaction two pairs of primers -synthetic oligonucleotides -were used; the oligonucleotide sequence in the primers and the PCR conditions were taken from the literature. 8,9 A 342 pb fragment was amplified as product of the PCR for the T102C polymorphism; it was then submitted to the restriction analysis (restriction fragment length polymorphism or RFLP) using the MspI enzyme (New England Biolabs) TM for 2:30 h at 37°C. 8 Digestion of the mutant homozygotic sample fragment (CC) for the T102C polymorphism (both mutant alleles) yields two fragments (217 pb and 125 pb) because of recognition of the Mspl enzyme restriction site by substitution of the T->C nitrogenated bases in the position 102 of the 5-HTR2A gene.…”

“…Thus, activation of these cell groups increases the activity of the genioglossus muscle. [7][8][9] It is evident that serotonin (5-hydroxytryptamine or 5-HT), a central nervous system neurotransmitter, is involved in regulating several visceral and physiologic functions such as sleep, appetite, thermoregulation, pain perception, hormone secretion, and sexual behavior. Changes in the serotonergic system have been implied in several human diseases such as depression, headaches, epilepsy, obsessive-compulsive behaviors, temporomandibular dysfunction, and affective disorders.…”

“…Changes in the serotonergic system have been implied in several human diseases such as depression, headaches, epilepsy, obsessive-compulsive behaviors, temporomandibular dysfunction, and affective disorders. [6][7][8][9] Serotonin also has a relevant role in upper airway patency, as it excites airway motor neurons and intrinsically excites the motor neurons in the brainstem. The activity of neurons that provide 5-HT to motor neurons declines with sleep; most of the functional studies have shown that 5-HT and serotonergic neurons exert a significant excitatory effect on respiratory motor neurons in vivo and in vitro.…”