Abstract
Objectives/Hypothesis: To evaluate the association of hypocretin neuropeptide precursor gene (HCRT) variations with obstructive sleep apnea syndrome (OSAS) in a cohort of Japanese patients and to further evaluate whether the significant HCRT variations have potential functional consequences on HCRT expression. Study Design: Case-control genetic association study. Methods: We studied the genetic variations within the HCRT gene. The study population consisted of 100 OSAS patients and 100 control subjects. The HCRT gene was amplified by polymerase chain reaction in all study subjects followed by direct sequencing and analysis of sequencing data. Results: Two genetic variations within the HCRT intron, IVS1+16T>C (rs9902709) and IVS1-69G>C, were identified with significant differences between patients and controls (P <.05). A reporter gene assay using HeLa cells showed that the construct containing the C allele of the rs9902709 variation had significantly higher luciferase activity compared with the construct containing the T allele (P =.002). Furthermore, enzyme immunoassay revealed that subjects with T/C and C/C genotypes for rs9902709 had 1.4-fold and 1.5-fold increases in sera levels of orexin-A, respectively. Conclusions: Our genetic association study, followed by functional and quantitative phenotyping assays, demonstrated a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS.
| Original language | English |
|---|---|
| Pages (from-to) | 925-929 |
| Number of pages | 5 |
| Journal | Laryngoscope |
| Volume | 122 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 01-04-2012 |
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All Science Journal Classification (ASJC) codes
- Otorhinolaryngology
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A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan. / Ahmed, Wael A.; Tsutsumi, Makiko; Nakata, Seiichi; Mori, Terumi; Nishimura, Yoichi; Fujisawa, Toshiyuki; Kato, Ichiro; Nakashima, Mayuki; Kurahashi, Hiroki; Suzuki, Kenji.
In: Laryngoscope, Vol. 122, No. 4, 01.04.2012, p. 925-929.Research output: Contribution to journal › Article
TY - JOUR
T1 - A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan
AU - Ahmed, Wael A.
AU - Tsutsumi, Makiko
AU - Nakata, Seiichi
AU - Mori, Terumi
AU - Nishimura, Yoichi
AU - Fujisawa, Toshiyuki
AU - Kato, Ichiro
AU - Nakashima, Mayuki
AU - Kurahashi, Hiroki
AU - Suzuki, Kenji
PY - 2012/4/1
Y1 - 2012/4/1
N2 - Objectives/Hypothesis: To evaluate the association of hypocretin neuropeptide precursor gene (HCRT) variations with obstructive sleep apnea syndrome (OSAS) in a cohort of Japanese patients and to further evaluate whether the significant HCRT variations have potential functional consequences on HCRT expression. Study Design: Case-control genetic association study. Methods: We studied the genetic variations within the HCRT gene. The study population consisted of 100 OSAS patients and 100 control subjects. The HCRT gene was amplified by polymerase chain reaction in all study subjects followed by direct sequencing and analysis of sequencing data. Results: Two genetic variations within the HCRT intron, IVS1+16T>C (rs9902709) and IVS1-69G>C, were identified with significant differences between patients and controls (P <.05). A reporter gene assay using HeLa cells showed that the construct containing the C allele of the rs9902709 variation had significantly higher luciferase activity compared with the construct containing the T allele (P =.002). Furthermore, enzyme immunoassay revealed that subjects with T/C and C/C genotypes for rs9902709 had 1.4-fold and 1.5-fold increases in sera levels of orexin-A, respectively. Conclusions: Our genetic association study, followed by functional and quantitative phenotyping assays, demonstrated a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS.
AB - Objectives/Hypothesis: To evaluate the association of hypocretin neuropeptide precursor gene (HCRT) variations with obstructive sleep apnea syndrome (OSAS) in a cohort of Japanese patients and to further evaluate whether the significant HCRT variations have potential functional consequences on HCRT expression. Study Design: Case-control genetic association study. Methods: We studied the genetic variations within the HCRT gene. The study population consisted of 100 OSAS patients and 100 control subjects. The HCRT gene was amplified by polymerase chain reaction in all study subjects followed by direct sequencing and analysis of sequencing data. Results: Two genetic variations within the HCRT intron, IVS1+16T>C (rs9902709) and IVS1-69G>C, were identified with significant differences between patients and controls (P <.05). A reporter gene assay using HeLa cells showed that the construct containing the C allele of the rs9902709 variation had significantly higher luciferase activity compared with the construct containing the T allele (P =.002). Furthermore, enzyme immunoassay revealed that subjects with T/C and C/C genotypes for rs9902709 had 1.4-fold and 1.5-fold increases in sera levels of orexin-A, respectively. Conclusions: Our genetic association study, followed by functional and quantitative phenotyping assays, demonstrated a functional locus within the HCRT gene, which may act to increase HCRT expression and lead to a protective effect against the development of OSAS.
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U2 - 10.1002/lary.23179
DO - 10.1002/lary.23179
M3 - Article
C2 - 22302634
AN - SCOPUS:84862815787
VL - 122
SP - 925
EP - 929
JO - Laryngoscope
JF - Laryngoscope
SN - 0023-852X
IS - 4
ER -