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Sleep disordered breathing and fibroblast growth factor 23 in the Hispanic Community Health Study/Study of Latinos.

TitleSleep disordered breathing and fibroblast growth factor 23 in the Hispanic Community Health Study/Study of Latinos.
Publication TypePublication
Year2018
AuthorsMehta R, Cai X, Hodakowski A, Thyagarajan B, Zeng D, Zee PC, Wohlgemuth WK, Redline S, Lash JP, Wolf M, Isakova T
JournalBone
Volume114
Pagination278-284
Date Published2018 09
ISSN1873-2763
KeywordsAdolescent, Adult, Aged, Biomarkers, Case-Control Studies, Cohort Studies, Female, Fibroblast Growth Factors, Hispanic Americans, Humans, Male, Middle Aged, Prospective Studies, Public Health, Sleep Apnea Syndromes, Young Adult
Abstract

Preclinical data suggest that hypoxia stimulates fibroblast growth factor 23 (FGF23) transcription and cleavage in osteocytes, resulting in elevated circulating c-terminal (cFGF23) levels but normal intact FGF23 (iFGF23) levels. We conducted a case-control study within the Hispanic Community Health Study/Study of Latinos to investigate whether sleep disordered breathing, as a model of hypoxemia, is independently associated with elevated cFGF23 levels in the general population and with elevated cFGF23 and iFGF23 levels in patients with chronic kidney disease (CKD), in whom FGF23 cleavage may be impaired. Cases (n = 602) had severe sleep disordered breathing defined as an apnea/hypopnea index (AHI) of ≥30. Controls without severe sleep disordered breathing (n = 602) were matched for sex and CKD stage. The median AHI in the cases was 45.8 (IQR 35.5-62.5) compared to 2.6 (IQR 0.6-8.2) in the controls. Cases had higher cFGF23 levels than controls (66.2 RU/mL, IQR 52.8-98.4 vs. 61.2 RU/mL, IQR 49.5-80.1, p value <0.001). There were no differences in iFGF23 levels between cases and controls. In adjusted linear regression and multinomial regression analyses, body mass index attenuated the relationship between severe sleep disordered breathing and cFGF23 levels. No significant relationships were seen in analyses of severe sleep disordered breathing and iFGF23 levels or in analyses of iFGF23 and cFGF23 stratified by CKD status. Additional studies using other models of intermittent and chronic hypoxia are needed to confirm whether hypoxia stimulates FGF23 transcription in humans and to determine the impact on iFGF23 levels in CKD.

DOI10.1016/j.bone.2018.06.024
Alternate JournalBone
PubMed ID29986841
PubMed Central IDPMC6785996
Grant ListN01 HC065234 / HC / NHLBI NIH HHS / United States
N01HC65236 / HL / NHLBI NIH HHS / United States
N01HC65235 / HL / NHLBI NIH HHS / United States
N01 HC065237 / HC / NHLBI NIH HHS / United States
R01 DK102438 / DK / NIDDK NIH HHS / United States
N01HC65234 / HL / NHLBI NIH HHS / United States
N01 HC065233 / HC / NHLBI NIH HHS / United States
N01HC65233 / HL / NHLBI NIH HHS / United States
N01HC65237 / HL / NHLBI NIH HHS / United States
N01 HC065236 / HC / NHLBI NIH HHS / United States
R01 DK081374 / DK / NIDDK NIH HHS / United States
K24 DK093723 / DK / NIDDK NIH HHS / United States
N01 HC065235 / HC / NHLBI NIH HHS / United States
MS#: 
0451
Manuscript Lead/Corresponding Author Affiliation: 
Ancillary Study Investigators - Not at HCHS/SOL site
ECI: 
Yes
Manuscript Status: 
Published