A functional variation in the hypocretin neuropeptide precursor gene may be associated with obstructive sleep apnea syndrome in Japan.

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.

Antimicrobial activities of tosufloxacin against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella branhamella catarrhalis isolated from otolaryngological infectious diseases.

In 2003, the Japan Society for Infectious Diseases in Otolaryngology conducted its third nationwide survey of clinical isolates from otolaryngological infectious diseases. We selected three primary causative organisms of otolaryngological infectious diseases, Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella Branhamella catarrhalis, and evaluated their sensitivities to tosufloxacin (TFLX), a new oral quinolone, because the survey revealed a rise in drug-resistant strains, suggesting potential problems with the antibiotics commonly used against these organisms. The minimum inhibitory concentration (MIC)(90) values of TFLX against S. pneumoniae, H. influenzae, and M. catarrhalis were 0.25 microg/ml,