Pilot cohort study on the potential role of <i><scp>TCF</scp>7L2</i> rs7903146 on ischemic heart disease among non‐diabetic kidney transplant recipients

Quaglia, Marco; Musetti, Claudio; Merlotti, Guido; Genazzani, Armando A.; Cargnin, Sarah; Cena, Tiziana; Cantaluppi, Vincenzo; Terrazzino, Salvatore

doi:10.1111/ctr.12959

Cited by 4 publications

(3 citation statements)

References 33 publications

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“…Because heart disease is a type of metabolic disorder, its association with TCF7L 2 warrants further investigation. Among nondiabetic kidney transplant recipients, the T allele at rs7903146 increases the risk of symptomatic coronary artery disease (CAD) and myocardial infarction 109 . rs12255372, rs7903146 and rs11196205 are also associated with CAD in patients with T2D 110 .…”

Section: Effects Of Tcf7l2 Variants In Other Metabolic Disordersmentioning

confidence: 99%

The role of transcription factor 7‐like 2 in metabolic disorders

Zhang

2020

Obesity Reviews

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Summary Transcription factor 7‐like 2 (TCF7L2), a member of the T cell factor/lymphoid enhancer factor family, generally forms a complex with β‐catenin to regulate the downstream target genes as an effector of the canonical Wnt signalling pathway. TCF7L2 plays a vital role in various biological processes and functions in many organs and tissues, including the liver, islet and adipose tissues. Further, TCF7L2 down‐regulates hepatic gluconeogenesis and promotes lipid accumulation. In islets, TCF7L2 not only affects the insulin secretion of the β‐cells but also has an impact on other cells. In addition, TCF7L2 influences adipogenesis in adipose tissues. Thus, an out‐of‐control TCF7L2 expression can result in metabolic disorders. The TCF7L2 gene is composed of 17 exons, generating 13 different transcripts, and has many single‐nucleotide polymorphisms (SNPs). The discovery that these SNPs have an impact on the risk of type 2 diabetes (T2D) has attracted thorough investigations in the study of TCF7L2. Apart from T2D, TCF7L2 SNPs are also associated with type 1, posttransplant and other types of diabetes. Furthermore, TCF7L2 variants affect the progression of other disorders, such as obesity, cancers, metabolic syndrome and heart diseases. Finally, the interaction between TCF7L2 variants and diet also needs to be investigated.

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Section: Effects Of Tcf7l2 Variants In Other Metabolic Disordersmentioning

confidence: 99%

The role of transcription factor 7‐like 2 in metabolic disorders

Zhang

2020

Obesity Reviews

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“…been investigated with large-scale GWAS approaches, although a handful of recent candidate gene studies have been published. [19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population. We therefore aimed to evaluate the predictive value of the risk score in RTRs by genotyping patients from the Assessment of Lescol in Renal Transplantation (ALERT) trial, 23,24 a study of mostly Caucasian, stable, and well-characterized RTRs followed for 7-8 years for validated clinical endpoints, including major cardiovascular events (MACEs).…”

Section: Genetic Variants In Relation To CV Outcome In Rtrs Have Not Yetmentioning

confidence: 99%

“…[19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population. [19][20][21][22] Given that etiologic factors explaining CV disease in RTRs might differ somewhat from those in the general population, one cannot automatically assume that the composite GRS investigated by Mega et al is valid for the transplant population.…”

Section: Introductionmentioning

confidence: 99%

Genetic markers associated with long-term cardiovascular outcome in kidney transplant recipients

Pihlstrøm

Mjøen

Mucha

et al. 2019

American Journal of Transplantation

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CorrespondenceHege Kampen Pihlstrøm Email: hegphi@ous-hf.no Funding information Novartis Pharma AGThere is a clear genetic contribution to the risk of cardiovascular diseases, and a composite genetic risk score (GRS) based on 27 single nucleotide polymorphisms (SNPs) was reported to predict risk of cardiovascular events in the general population. We aimed to evaluate this risk score in renal transplant recipients, a population with heightened cardiovascular risk, with a yet unknown genetic contribution. A total of 1640 participants from the ALERT trial (Assessment of Lescol in Renal Transplantation), a study comparing fluvastatin with placebo in stable renal transplant recipients, were genotyped for all SNPs making up the GRS. Risk alleles were weighted by the log of odds ratios reported in genome wide association studies and summed. Associations between GRS and time from study inclusion to first major cardiovascular event (MACE) were analyzed by Cox regression. In analyses adjusted for cardiovascular risk factors, GRS was significantly associated with MACE (hazard ratio [HR] 1.81, P = .006) when comparing genetic high-risk patients (quartile 4) with genetic low-risk participants (quartile 1). A 27-SNP GRS, which predicted cardiovascular events in the nontransplant population, appears to have predictive value also in kidney allograft recipients. Refining the score to better fit the transplant population seems feasible. K E Y W O R D Sbiomarker, clinical research/practice, coronary artery disease, epidemiology, genetics, kidney transplantation/nephrology, risk assessment/risk stratification, translational research/science

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