Role of patatin-like phospholipase domain-containing 3 gene for decreasing kidney function in recently diagnosed diabetes mellitus.

Diabetes Metab Syndr

Department of Endocrinology and Diabetology, Medical Faculty and University Hospital, Heinrich Heine University, Düsseldorf, Germany; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Institute for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany; German Center

Published: October 2024


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Article Abstract

Aims: We examined the association of the G allele in the single-nucleotide polymorphism (SNP) rs738409 in the third exon of patatin-like phospholipase domain-containing 3 gene (PNPLA3) gene, with chronic kidney disease in diabetes endotypes.

Methods: Participants with recent-onset diabetes (n = 707) from the prospective German Diabetes Study (GDS) underwent cluster assignment, detailed phenotyping, genotyping and magnetic resonance spectroscopy to quantify hepatocellular lipid content (HCL).

Results: Severe insulin-resistant diabetes (SIRD) had the lowest glomerular filtration rates (eGFR) and highest HCL compared to severe insulin-deficient, moderate obesity-related, moderate age-related and severe autoimmune diabetes endotypes (all p < 0.05). HCL was negatively associated with eGFR (r = -0.287, p < 0.01) across all groups. Stratification by G-allele carrier status did not reveal any association between HCL and eGFR among the endotypes. However, the proportion of G-allele carriers increased from 44 % for eGFR >60 ml/min to 52 % for eGFR <60 ml/min (p < 0.05).

Conclusions: The PNPLA3 polymorphism may contribute to declining kidney function independently of liver lipids.

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http://dx.doi.org/10.1016/j.dsx.2024.103137DOI Listing

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