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Clin Transplant. 2017 Jun;31(6). doi: 10.1111/ctr.12959. Epub 2017 Apr 17.

Pilot cohort study on the potential role of TCF7L2 rs7903146 on ischemic heart disease among non-diabetic kidney transplant recipients.

Author information

1
Department of Translational Medicine, Nephrology and Kidney Transplant Unit, University of Piemonte Orientale, Novara, Italy.
2
Dipartimento di Scienze del Farmaco & Centro di Ricerca Interdipartimentale di Farmacogenetica e Farmacogenomica (CRIFF), University of Piemonte Orientale, Novara, Italy.
3
Unit of Medical Statistics and Cancer Epidemiology, University of Piemonte Orientale and CPO Piemonte, Novara, Italy.

Abstract

BACKGROUND:

TCF7L2 rs7903146 C>T polymorphism is associated with diabetes in the general population but its independent impact on cardiovascular disease is debated. On this basis, we investigated its association with major adverse cardiac events (MACE) in a single-center cohort of non-diabetic kidney transplant recipients (KTRs).

METHODS:

Patients with pretransplant diabetes were excluded and patients who developed post-transplant diabetes were censored at time of diagnosis.

RESULTS:

rs7903146 C>T polymorphism appeared to modulate the risk of MACE: 5-year prevalence was 0.8% in CC patients, 7.2% in CT patients and 9.7% in TT patients (P<.001). TCF7L2 rs7903146 was an independent predictor of MACE in a multivariate Cox regression model (for each T allele, HR: 2.99, 95%CI: 1.62-5.52, P<.001), together with history of cardiac ischemic events (HR: 8.69, 95%CI: 3.57-21.16, P<.001), DGF (HR: 2.42, 95%CI: 0.98-5.95, P=.056) and HLA-mismatches (for each mismatch: HR: 1.55, 95%CI: 1.00-2.43, P=.053). Introduction of rs7903146 C>T polymorphism into a model based on these clinical variables significantly increased predictive power for MACE (P=.003).

CONCLUSIONS:

TCF7L2 rs7903146 T allele may be strongly and independently associated with MACE in non-diabetic KTRs. These findings suggest the possibility of employing this SNP to more accurately stratify cardiological risk in KTRs.

KEYWORDS:

TCF7L2; acute myocardial infarction; coronary artery disease; coronary heart disease; kidney transplantation; rs7903146

PMID:
28299838
DOI:
10.1111/ctr.12959
[Indexed for MEDLINE]

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