The Importance of the FUT2 rs602662 Polymorphism in the Risk of Cardiovascular Complications in Patients after Kidney Transplantation

Author:

Kotowski Maciej Józef1ORCID,Ostrowski Piotr1ORCID,Sieńko Jerzy2,Czerny Bogusław34,Tejchman Karol1ORCID,Machaliński Bogusław5,Górska Aleksandra3,Mrozikiewicz Aleksandra E.6,Bogacz Anna7ORCID

Affiliation:

1. Department of General Surgery and Transplantology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland

2. Institute of Physical Culture Sciences, University of Szczecin, 70-453 Szczecin, Poland

3. Department of Stem Cells and Regenerative Medicine, Institute of Natural Fibres and Medicinal Plants, Kolejowa 2, 62-064 Plewiska, Poland

4. Department of Pharmacology and Pharmacoeconomics, Pomeranian Medical University in Szczecin, Żołnierska 48, 71-230 Szczecin, Poland

5. Department of General Pathology, Pomeranian Medical University in Szczecin, 70-111 Szczecin, Poland

6. Department of Obstetrics and Women’s Diseases, Poznan University of Medical Sciences, Polna 33, 60-535 Poznan, Poland

7. Department of Personalized Medicine and Cell Therapy, Regional Blood Center, Marcelińska 44, 60-354 Poznan, Poland

Abstract

The FUT2 gene encodes an enzyme called α-1,2-fucosyltransferase, which is involved in the formation of blood group antigens AB0(H) and is also involved in the processes of vitamin B12 absorption and its transport between cells. FUT2 gene polymorphisms are associated with vitamin B12 levels in the body. Vitamin B12 deficiency associated with hyperhomocysteinemia is a major risk factor for cardiovascular diseases (CVDs), which are one of the main causes of death in patients after kidney transplantation. The aim of our study was to determine the impact of the rs602662 (G>A) polymorphism of the FUT2 gene on the functionality of transplanted kidneys and the risk of CVD in patients after kidney transplantation. The study included 402 patients treated with immunosuppression (183 patients taking cyclosporine (CsA) and 219 patients taking tacrolimus (TAC)). The analysis of the FUT2 rs602662 (G>A) polymorphism was performed using real-time PCR. Patients with CsA were more likely to be underweight (1.64% vs. 0.91%) and obese (27.87% vs. 15.98%), while those taking TAC were more likely to be of normal weight (39.27%) or overweight (43.84%). No statistically significant differences were observed comparing the mean blood pressure, both systolic and diastolic. The renal profile showed a higher median urea nitrogen concentration in patients with CsA (26.45 mg/dL (20.60–35.40) vs. 22.95 mg/dL (17.60–33.30), p = 0.004). The observed frequency of rs602662 alleles of the FUT2 gene was similar in the analyzed groups. The A allele was present in 43.7% of patients with CsA and 41.1% of those taking TAC (OR = 0.898; 95% CI: 0.678–1.189; p = 0.453). In the group with CsA, the GG genotype was present in 32.2% of patients, the GA in 48.1% and the AA in 19.7%. A similar distribution was obtained in the TAC group: GG—33.8%, GA—50.2%, and AA—16.0%. An association of genotypes containing the G allele with a higher incidence of hypertension was observed. The G allele was present in 65% of people with hypertension and in 56% of patients with normal blood pressure (p = 0.036). Moreover, the evaluation of the renal parameters showed no effect of the FUT2 polymorphism on the risk of organ rejection because the levels of creatinine, eGFR, potassium, and urea nitrogen were prognostic of successful transplantation. Our results suggest that the rs6022662 FUT2 polymorphism may influence the risk of cardiovascular diseases.

Funder

National Science Centre

Publisher

MDPI AG

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