ASN's Mission

To create a world without kidney diseases, the ASN Alliance for Kidney Health elevates care by educating and informing, driving breakthroughs and innovation, and advocating for policies that create transformative changes in kidney medicine throughout the world.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: TH-PO246

Phenome-Wide Association Study of Common Genetic Variants in the DPP4 Gene and GLP1R Gene and Kidney Outcomes of European Ancestry Individuals in the Million Veteran Program (MVP)

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Triozzi, Jefferson Lorenzo, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Chen, Hua-Chang, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Tao, Ran, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wilson, Otis D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Wang, Guanchao, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Ikizler, Talat Alp, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Bick, Alexander, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Siew, Edward D., Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Robinson-Cohen, Cassianne, Vanderbilt University Medical Center, Nashville, Tennessee, United States
  • Hung, Adriana, Vanderbilt University Medical Center, Nashville, Tennessee, United States

Group or Team Name

  • Million Veteran Program
Background

Incretin mimetics, including dipeptidyl-peptidase 4 inhibitors and glucagon-like peptide 1 receptor agonists, are antihyperglycemic agents that activate neurohormonal pathways to suppress appetite and increase glucagon secretion. Although incretin mimetics are associated with glucose control and improved cardiovascular outcomes, their effect on kidney outcomes is not clearly demonstrated.

Methods

We tested the association of one single nucleotide polymorphism (SNP) in the DDP4 gene encoding dipeptidyl peptidase 4 (rs11695223 [intronic]) and two SNPs in the GLP1R gene encoding glucagon-like peptide 1 hormone receptor (rs1030505420 [missense], rs2268647 [intronic]) in a phenome-wide association study (PheWAS) using electronic health record data from European ancestry individuals in the MVP. The GLP1R variants are considered drug proxies for agonism. We mapped 1311 clinical diagnoses based on ICD-codes using PheWAS methodology in up to 458,165 individuals of European ancestry. PheWAS was performed by fitting logistic regression models adjusting for age, sex, and ten principal components of ancestry, regressed against the SNPs of interest. Level of significance was set using Bonferroni at 0.05/1311 or p=3.81E-05.

Results

The DPP4 variant was associated with multiple ICD-codes for kidney disease with PheWAS significance. The GLP1R variants did not reach PheWAS significance (Table 1).

Conclusion

Our study shows that the DPP4 SNP is associated with kidney outcomes, including ESRD, CKD, urinary calculus, and microscopic hematuria. The GLP1R SNPs were associated with T2DM with renal manifestations and CKD, but these did not reach PheWAS significance. Further study is needed to elucidate mechanisms by which incretin pathways affect kidney outcomes.

Funding

  • Veterans Affairs Support