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

Diabetes Metab Syndr. 2024 Oct;18(10):103137. doi: 10.1016/j.dsx.2024.103137. Epub 2024 Oct 14.

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.

Keywords: Genetic variant; Nephropathy; Steatosis.

MeSH terms

  • Acyltransferases
  • Adult
  • Biomarkers / analysis
  • Diabetes Mellitus, Type 2 / genetics
  • Female
  • Follow-Up Studies
  • Genotype
  • Glomerular Filtration Rate*
  • Humans
  • Insulin Resistance / genetics
  • Lipase* / genetics
  • Male
  • Membrane Proteins* / genetics
  • Middle Aged
  • Phospholipases A2, Calcium-Independent
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Prospective Studies
  • Renal Insufficiency, Chronic / genetics

Substances

  • Lipase
  • PNPLA3 protein, human
  • Membrane Proteins
  • Biomarkers
  • Acyltransferases
  • Phospholipases A2, Calcium-Independent