|Title||Variants, N-Acetylated Amino Acids, and Progression of CKD.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Luo S, Surapaneni A, Zheng Z, Rhee EP, Coresh J, Hung AM, Nadkarni GN, Yu B, Boerwinkle E, Tin A, Arking DE, Steinbrenner I, Schlosser P, Köttgen A, Grams ME|
|Journal||Clin J Am Soc Nephrol|
|Date Published||2020 Dec 31|
BACKGROUND AND OBJECTIVES: Genetic variants in , a liver- and kidney-specific acetyltransferase encoding gene, have been associated with eGFR and CKD in European populations. Higher circulating levels of two -associated metabolites, N--acetylornithine and N-acetyl-1-methylhistidine, have been linked to lower eGFR and higher risk of incident CKD in the Black population. We aimed to expand upon prior studies to investigate associations between rs13538, a missense variant in , N-acetylated amino acids, and kidney failure in multiple, well-characterized cohorts.
DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted analyses among participants with genetic and/or serum metabolomic data in the African American Study of Kidney Disease and Hypertension (AASK; =962), the Atherosclerosis Risk in Communities (ARIC) study (=1050), and Bio, an electronic health record-linked biorepository (=680). Separately, we evaluated associations between rs13538, urinary N-acetylated amino acids, and kidney failure in participants in the German CKD (GCKD) study (=1624).
RESULTS: Of 31 N-acetylated amino acids evaluated, the circulating and urinary levels of 14 were associated with rs13538 (
CONCLUSIONS: We demonstrate significant associations between an gene variant and 14 N-acetylated amino acids, five of which had circulation levels that were associated with kidney failure.
|Alternate Journal||Clin J Am Soc Nephrol|
|PubMed Central ID||PMC7792648|
|Grant List||R01 DK108803 / DK / NIDDK NIH HHS / United States|