The HMOX2 polymorphism contributes to the carotid body chemoreflex in European sea-level residents by regulating hypoxic ventilatory responses.

This study investigates whether a functional single nucleotide polymorphism of HMOX2 (heme oxygenase-2) (rs4786504 T>C) is involved in individual chemosensitivity to acute hypoxia, as assessed by ventilatory responses, in European individuals. These responses were obtained at rest and during submaximal exercise, using a standardized and validated protocol for exposure to acute normobaric hypoxia. Carriers of the ancestral T allele (n = 44) have significantly lower resting and exercise hypoxic ventilatory responses than C/C homozygous carriers (n = 40). In the literature, a hypoxic ventilatory response threshold to exercise has been identified as an independent predictor of severe high altitude-illness (SHAI). Our study shows that carriers of the T allele have a higher risk of SHAI than carriers of the mutated C/C genotype. Secondarily, we were also interested in COMT (rs4680 G > A) polymorphism, which may be indirectly involved in the chemoreflex response through modulation of autonomic nervous system activity. Significant differences are present between COMT genotypes for oxygen saturation and ventilatory responses to hypoxia at rest. In conclusion, this study adds information on genetic factors involved in individual vulnerability to acute hypoxia and supports the critical role of the ≪ O2 sensor ≫ - heme oxygenase-2 - in the chemosensitivity of carotid bodies in Humans.

Genetic Determinants of Neurobehavioral Responses to Caffeine Administration during Sleep Deprivation: A Randomized, Cross Over Study (NCT03859882).

This study investigated whether four single nucleotide polymorphisms (SNPs) moderated caffeine effects on vigilance and performance in a double-blind and crossover total sleep deprivation (TSD) protocol in 37 subjects. In caffeine (2 × 2.5 mg/kg/24 h) or placebo-controlled condition, subjects performed a psychomotor vigilance test (PVT) and reported sleepiness every six hours (Karolinska sleepiness scale (KSS)) during TSD. EEG was also analyzed during the 09:15 PVT. Carriers of the TNF-α SNP A allele appear to be more sensitive than homozygote G/G genotype to an attenuating effect of caffeine on PVT lapses during sleep deprivation only because they seem more degraded, but they do not perform better as a result. The A allele carriers of COMT were also more degraded and sensitive to caffeine than G/G genotype after 20 h of sleep deprivation, but not after 26 and 32 h. Regarding PVT reaction time, ADORA2A influences the TSD effect but not caffeine, and PER3 modulates only the caffeine effect. Higher EEG theta activity related to sleep deprivation was observed in mutated TNF-α, PER3, and COMT carriers, in the placebo condition particularly. In conclusion, there are genetic influences on neurobehavioral impairments related to TSD that appear to be attenuated by caffeine administration. (NCT03859882).

Genotyping on blood and buccal cells using loop-mediated isothermal amplification in healthy humans.

Genetic variations contribute to phenotypic individual vulnerabilities to sleep debt, particularly for five single nucleotide polymorphisms (SNPs). Loop-mediated isothermal amplification and melting curve analysis (LAMP-MC) is a recently developed method to characterize SNPs. The aim of present study was to evaluate the LAMP-MC method on blood and buccal cells for detection of five SNPs of interest in healthy humans. We first analyzed signals obtained from LAMP-MC method on 42 samples. Then we compared the results with those of referent TaqMan method. The LAMP-MC method produced specific melting curves for the five SNPs. A high concordance of genotyping results was observed between the two methods for rs5751876_ADORA2A, rs1800629_TNF-α, rs73598374_ADA and rs228697_PER3 in blood and saliva (Cohen's kappa coefficient >0.80). A good agreement ( = 0.61) was observed for rs4680_COMT in blood only. LAMP-MC is a simple and reliable method to study genetic influences on health, sleep debt-related performance impairments and countermeasures.