Insulin receptor substrate gene polymorphism is associated with obstructive sleep apnea syndrome in men.

OBJECTIVE: The objective of this study was to assess significance of insulin receptor substrate (IRS) -1 gene polymorphism (Gly972Arg) at codon 972 in obstructive sleep apnea syndrome (OSAS). METHODS: Using the polymerase chain reaction technique, the codon 972 polymorphism of the IRS-1 gene was analyzed in the DNA obtained from leukocytes of 50 patients and 143 healthy controls. RESULTS: An overall comparison between the genotypes and allele frequencies of the patients and controls did not reveal any statistically significant difference between the patients and controls (P > .05). Gender-specific comparisons were not significantly different except for a significant difference between the genotypes and allele frequencies of the male patients and male controls (P < .05). The heterozygous, Gly/Arg variant of the IRS-1 gene was overrepresented and the homozygous, Gly/Gly variant was less frequent in male patients compared with male controls. In the patients with OSAS, there was no correlation between the genotypes and polysomnography parameters on correlation analyses (P > .05). There was no relationship between the genotypes and diabetes mellitus (P > .05). Body mass indices and polysomnography parameters of the patients with and without diabetes mellitus were not significantly different (P > .05). CONCLUSION: The polymorphism of the IRS-1 gene at codon 972, especially Gly/Arg variant, or the presence of the allele for Arg appears to be associated with occurrence of OSAS in male patients, whereas this polymorphism is not related to severity of OSAS.

Association of GABA(B)R1 receptor gene polymorphism with obstructive sleep apnea syndrome.

OBJECTIVE: GABA(B)R (gamma-amino butyric acid B receptor)-mediated neurotransmission has been implicated in the pathophysiology of a variety of neuropsychiatric disorders. GABA(B)R1 gene variants were identified by single-strand conformation analysis. The nucleotide exchanges cause a substitution of alanine to valine in exon 1a1 (Ala20Val), a substitution of glycine to serine in exon 7 (Gly489Ser) and a silent C to G nucleotide exchange encoding the amino acid phenylalanine in exon 11 (Phe658Phe). The significance of GABA(B)R1a gene polymorphism in obstructive sleep apnea syndrome (OSAS) as well as the association of these polymorphisms with the polysomnography findings in OSAS patients are not known. In this study, we aimed to assess the significance of 3 different GABA(B)R1 gene polymorphisms (Ala20Val, Gly489Ser and Phe658Phe) in OSAS. METHODS: Seventy-five patients (23 female and 52 male) with OSAS and 99 healthy volunteers (51 female, 48 male) were included in the study to assess Ala20Val, Gly489Ser and Phe658Phe polymorphisms of the GABA(B)R1 gene. RESULTS: For the Ala20Val variants, there was no significant difference between the genotypes and allele frequencies of the patients and controls, nor between both genders (p > 0.05). For Phe658Phe polymorphism, there was no significant difference between genotypes and allele frequencies of the patients and controls (p > 0.05). However, the C/C genotype was overrepresented and the T/C genotype was less frequent in male than female patients (p = 0.03). The C/C genotype was overrepresented and the T/C genotype was less frequent in male patients than male controls (p = 0.01). For GABA(B)R1-Gly489Ser polymorphism, all of the patients and controls had G/G genotype. The apnea arousal index scores of the male patients with C/C genotype were significantly higher than in the patients with C/T genotype (p = 0.01). The percent total sleep time in non-REM 1 scores of the male patients with T/T genotype were significantly higher than in the patients with T/C genotype (p = 0.021). The percent total sleep time in non-REM 2 scores of the female patients with C/C genotype were significantly higher than in the patients with C/T genotype (p = 0.006). CONCLUSION: The Ala20Val polymorphism of the GABA(B)R1 gene may be associated with OSAS, whereas Gly489Ser polymorphism does not seem to be involved in OSAS. The C/C variant of the Phe658Phe polymorphism GABA(B)R1 gene seems associated with the occurrence of OSAS and is also associated with some sleep related parameters (apnea arousal index and percent total sleep time in non-REM) recorded by polysomnography.

Association of the -1438G/A polymorphism of the 5-HT2A receptor gene with obstructive sleep apnea syndrome.

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-HT2A 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-HT2A 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-HT2A 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.