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Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

Investigating Genetic Determinants of Plasma Inositol Status in Adult Humans

Authors :
Eleanor Weston
Faith Pangilinan
Simon Eaton
Michael Orford
Kit-Yi Leung
Andrew J Copp
James L Mills
Anne M Molloy
Lawrence C Brody
Nicholas DE Greene
Source :
The Journal of nutrition.
Publication Year :
2022

Abstract

Myo-inositol (MI) is incorporated into numerous biomolecules, including phosphoinositides and inositol phosphates. Disturbance of inositol availability or metabolism is associated with various disorders, including neurological conditions and cancers, while supplemental MI has therapeutic potential in conditions such as depression, polycystic ovary syndrome and congenital anomalies. Inositol status may be influenced by diet, synthesis, transport, utilisation and catabolism.We aimed to investigate potential genetic regulation of circulating MI status and to evaluate correlation of MI concentration with other metabolites.Gas chromatography mass spectrometry was used to determine plasma MI concentration of more than 2,000 healthy, young adults (aged 18-28 years) from the Trinity Student Study. Genotyping data was used to test association of plasma MI with SNPs in candidate genes, encoding inositol transporters and synthesising enzymes, and test for genome-wide association. We evaluated potential correlation of plasma MI with D-chiro inositol, glucose and other metabolites by Spearman's rank correlation.Mean plasma MI showed a small but significant difference between males and females (28.5 and 26.9 µM, respectively). Candidate gene analysis revealed several nominally significant associations with plasma MI, most notably for SLC5A11, encoding a sodium-coupled inositol transporter, also known as SMIT2 (sodium-dependent myo-inositol transporter 2). However, these did not survive correction for multiple testing. Subsequent testing for genome-wide association with plasma MI did not identify associations of genome-wide significance (p 5 × 10-8). However, 8 SNPs exceeded the threshold for suggestive significant association with plasma MI concentration (p 1 × 10-5), 3 of which were located within or close to genes: MTDH, LAPTM4B and ZP2. We found significant positive correlation of plasma MI concentration with concentration of D-chiro-inositol and several other biochemicals including glucose, methionine, betaine, sarcosine and tryptophan.Our findings suggest potential for modulation of plasma MI in young adults by variation in SLC5A11 which is worthy of further investigation.

Details

ISSN :
15416100
Database :
OpenAIRE
Journal :
The Journal of nutrition
Accession number :
edsair.doi.dedup.....7603a2e0c700aa7dfaecea329e0792b5