Effect of metabolic genetic variants on long-term disease comorbidity in patients with type 2 diabetes

Shifteh Abedian, Ali Abbasi, Anthonius de Boer, Bruno H. Stricker, Stephan J.L. Bakker, Pim van der Harst, Sanaz Sedaghat, Maryam Darvishian, M. Arfan Ikram, Gerjan Navis, Abbas Dehghan, Ido Pen, Ronald P. Stolk, Harold Snieder, Olaf H. Klungel, Patrick Souverein, Behrooz Z. Alizadeh

Research output: Contribution to journalArticlepeer-review

Abstract

Underlying genetic determinants contribute to developing type 2 diabetes (T2D) future diseases. The present study aimed to identify which genetic variants are associated with the incident of the major T2D co-morbid disease. First, we conducted a discovery study by investigating the genetic associations of comorbid diseases within the framework of the Utrecht Cardiovascular Pharmacogenetic studies by turning information of > 25 years follow-up data of 1237 subjects whom were genotyped and included in the discovery study. We performed Cox proportional-hazards regression to examine associations between genetic variants and comorbid diseases including cardiovascular diseases (CVD), chronic eye disease, cancer, neurologic diseases and chronic kidney disease. Secondly, we replicated our findings in two independent cohorts consisting of 1041 subjects. Finally, we performed a meta-analysis by combining the discovery and two replication cohorts. We ascertained 390 (39.7%) incident cases of CVD, 182 (16.2%) of chronic eye disease, 155 (13.8%) of cancer, 31 (2.7%) of neurologic disease and 13 (1.1%) of chronic kidney disease during a median follow-up of 10.2 years. In the discovery study, we identified a total of 39 Single Nucleotide Polymorphisms (SNPs) associated with comorbid diseases. The replication study, confirmed that rs1870849 and rs8051326 may play a role in the incidence of chronic eye disease in T2D patients. Half of patients developed at least one comorbid disease, with CVD occurring most often and earliest followed by chronic eye disease. Further research is needed to confirm the associations of two associated SNPs with chronic eye disease in T2D.

Original languageEnglish (US)
Article number2794
JournalScientific reports
Volume11
Issue number1
DOIs
StatePublished - Dec 2021

Bibliographical note

Funding Information:
This work was supported by the Netherlands Heart Foundation, Dutch Diabetes Research Foundation, Dutch Kidney Foundation and the Netherlands Organization for Scientific Research project (NWO). This research was performed within the framework of CTMM, the Center for Translational Molecular Medicine (www.ctmm.nl); project predicts (grant 01C-104–07). None of the study sponsors had a role in the study design, data collection, analysis and interpretation, report writing, or the decision to submit the report for publication.

Funding Information:
This work was supported by the Netherlands Heart Foundation, the Dutch Diabetes Research Foundation, and the Dutch Kidney Foundation. This research was performed within the framework of the Center for Translational Molecular Medicine (CTMM; www.ctmm.nl); project predicts (grant 01C-104-07).

Publisher Copyright:
© 2021, The Author(s).

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