Send to

Choose Destination
PLoS One. 2017 Jan 3;12(1):e0168930. doi: 10.1371/journal.pone.0168930. eCollection 2017.

Analysis of Hypoxic and Hypercapnic Ventilatory Response in Healthy Volunteers.

Author information

Pediatric Pulmonology Unit, Shaare Zedek Medical Center, Hebrew University, School of Medicine, Jerusalem, Israel.
Stanford University Center for Sleep Sciences, Palo Alto, CA, United States of America.
East London NHS Foundation Trust, Newham Centre for Mental Health, London, United Kingdom.
Neuropediatric unit, Shaare Zedek Medical Center, Hebrew University, School of Medicine, Jerusalem, Israel.
Department of Family Medicine, Hebrew University and Clalit Health Services, Jerusalem, Israel.
Department of Pulmonary Medicine, Peking University People's Hospital, Beijing, China.



A previous study has suggested that the Human Leukocyte Antigen (HLA) allele DQB1*06:02 affects hypoxic ventilatory response (HVR) but not hypercapnic ventilatory response (HCVR) in an Asian population. The current study evaluated the relationship in Caucasians and Asians. In addition we assessed whether gender or polymorphisms in genes participating in the control of breathing affect HVR and HCVR.


A re-breathing system was used to measure HVR and HCVR in 551 young adults (56.8% Caucasians, 30% Asians). HLA-DQB1*06:02 and tagged polymorphisms and coding variants in genes participating in breathing (PHOX2B, GPR4 and TASK2/KCNK5) were analyzed. The associations between HVR/HCVR and HLA-DQB1*06:02, genetic polymorphisms, and gender were evaluated using ANOVA or frequentist association testing with SNPTEST.


HVR and gender are strongly correlated. HCVR and gender are not. Mean HVR in women was 0.276±0.168 (liter/minute/%SpO2) compared to 0.429±0.266 (liter/minute/%SpO2) in men, p<0.001 (55.4% higher HVR in men). Women had lower baseline minute ventilation (8.08±2.36 l/m vs. 10.00±3.43l/m, p<0.001), higher SpO2 (98.0±1.3% vs. 96.6±1.7%, p<0.001), and lower EtCO2 (4.65±0.68% vs. 4.82±1.02%, p = 0.025). One hundred and two (18.5%) of the participants had HLA-DQB1*06:02. No association was seen between HLA-DQB1*06:02 and HVR or HCVR. Genetic analysis revealed point wise, uncorrected significant associations between two TASK2/KCNK5 variants (rs2815118 and rs150380866) and HCVR.


This is the largest study to date reporting the relationship between gender and HVR/ HCVR and the first study assessing the association between genetic polymorphisms in humans and HVR/HCVR. The data suggest that gender has a large effect on hypoxic breathing response.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center