N-Lactoyl amino acids: insights from metabolite genome-wide association studies and phenome-wide association analysis

<p dir="ltr">N-lactoyl-amino acids (Lac-AA) are emerging as important metabolites with diverse physiological roles. This study integrates metabolomics and genomics to investigate the genetic determinants and clinical relevance of three Lac-AA: N-Lactoyl phenylalanine (Lac-Phe), N-Lac...

وصف كامل

محفوظ في:
التفاصيل البيبلوغرافية
المؤلف الرئيسي: Asma A Elashi (18464133) (author)
مؤلفون آخرون: Aleem Razzaq (14779189) (author), Najeha Anwardeen (11924495) (author), Khaled Naja (17886740) (author), Mashael Alshafai (14778607) (author), Ilhame Diboun (3522413) (author), Omar Albagha (8977856) (author), Mohamed A Elrayess (11843435) (author)
منشور في: 2025
الموضوعات:
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الوصف
الملخص:<p dir="ltr">N-lactoyl-amino acids (Lac-AA) are emerging as important metabolites with diverse physiological roles. This study integrates metabolomics and genomics to investigate the genetic determinants and clinical relevance of three Lac-AA: N-Lactoyl phenylalanine (Lac-Phe), N-Lactoyl tyrosine (Lac-Tyr), and N-Lactoyl valine (Lac-Tyr). We conducted a metabolome-wide association study (mGWAS) on 2811 participants followed by a phenome-wide association study (PheWAS) and pathway enrichment analysis. Our mGWAS revealed modest genetic contributions to Lac-AA levels, with genome-wide significant loci identified for Lac-Tyr and Lac-Val, but not for Lac-Phe. PheWAS analysis linked these genetic variants to key clinical traits, including white blood cell count, platelet count, and glucose levels. Pathway enrichment highlighted the involvement of Lac-AA in immune-metabolic crosstalk, particularly in inflammation and energy metabolism. These findings suggest that Lac-AA levels are primarily influenced by dynamic metabolic or inflammatory states rather than fixed genetic factors. Our results underscore the potential of Lac-AA as metabolic sensors and biomarkers at the intersection of cellular energy states and systemic inflammation, opening new avenues for research in metabolic and inflammatory disorders.</p><h2 dir="ltr">Other Information</h2><p dir="ltr">Published in: Human Molecular Genetics<br>License: <a href="https://creativecommons.org/licenses/by/4.0/" target="_blank">https://creativecommons.org/licenses/by/4.0/</a><br>See article on publisher's website: <a href="https://dx.doi.org/10.1093/hmg/ddaf152" target="_blank">https://dx.doi.org/10.1093/hmg/ddaf152</a></p>