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Abstract: FR-PO432

TCF7L2 and ACE Polymorphisms Confer Genetic Susceptibility to Diabetes Mellitus Type 2/Diabetic Nephropathy in Chilean Patients

Session Information

Category: Diabetic Kidney Disease

  • 602 Diabetic Kidney Disease: Clinical

Authors

  • Krall, Paola, Universidad Austral de Chile, Valdivia, Chile
  • Peralta, Natalia Carolina, Universidad Austral de Chile, Valdivia, Chile
  • Nualart, Daniela Paz, Universidad Austral de Chile, Valdivia, Chile
  • Lavoz, Carolina, Universidad Austral de Chile, Valdivia, Chile
  • Elgueta, Osvaldo A., Cesfam Externo Valdivia, Valdivia, Chile
  • Ardiles, Leopoldo G., Universidad Austral de Chile, Valdivia, Chile
  • Flores, Claudio A., Universidad Austral de Chile, Valdivia, Chile
  • Mezzano, Sergio A., Universidad Austral de Chile, Valdivia, Chile
Background

Diabetes mellitus type 2 (DMT2) is a chronic disease that is the leading cause of end-stage renal disease due to diabetic nephropathy (DN). A role in DN has been described for Gremlin (GREM1) and for an indel (I/D) in the Angiotensin-converting-enzyme (ACE) gene. Chile has the highest prevalence of DMT2 in Latin America, but the genetic susceptibility to develop DMT2 or DN remains undetermined. The aim of this work is to explore in a cohort of Chilean subjects, the association of polymorphisms in genes related to GREM1 and ACE with DMT2 or DN.

Methods

A retrospective case-control study was performed in 140 control subjects and DMT2 patients without DN (n=80) or with DN (n=101), categorized as those with early DN (1-7 yrs after DMT2 diagnosis) and late DN (8-15 yrs after DMT2 diagnosis). The genotype in the following polymorphisms was determined: rs1129456 (GREM1), rs7903146 (TCF7L2), rs34231037 (VEGFR2), rs4819554 (IL-17RA), indel (18 pb) in the VEGF gene and the indel (~300pb) in the ACE gene. Allelic and genotypic frequencies were analyzed to determine Odds ratio (OR).

Results

The analysis showed that the T allele (TCF7L2) was associated with DMT2 (OR=1.53, IC 95%=1.08-2.18, p=0.009). Additionally, a significant association was identified between the D allele (ACE) and the development of DN (OR=1.62, IC 95%=1.06-2.47, p=0.01), as well as with an early development of DN (OR=2.22, IC 95%= 1.10- 4.46, p=0.01).

Conclusion

Our results demonstrate that particular variants in TCF7L2 (T allele) and ACE (D allele) are highly prevalent in the study cohort (30-50%) and present a potential clinical value as risk alleles for DMT2 and DN of early development. TCF7L2 is a transcription factor controlling the GREM1 expression. Although the SNP in GREM1 was not associated with DMT2/ DN, further studies are required to determine if the TCF7L2 genotype is associated with GREM1 expression in the diabetic kidney. A larger study with multi-center individuals’ recruitment is required to validate TCF7L2 and ACE as genetic markers of susceptibility in the Chilean population, in order to consider them as input to design more effective strategies to prevent DMT2 and DN. Grant FONDECYT Regular 116-0465

Funding

  • Government Support - Non-U.S.