FTO Gene Polymorphisms and Their Roles in Acromegaly

Int J Mol Sci. 2023 Jun 30;24(13):10974. doi: 10.3390/ijms241310974.

Abstract

The major causes of both morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVDs). The polymorphisms of the fat mass and obesity-associated gene (FTO) are associated with obesity, as well as with an increased risk of CVDs. The aim of the study was to determine the relationship of risk alleles of four FTO gene polymorphisms with selected parameters of lipid and glucose metabolism as well as with IGF-1 and GH levels in the group of patients with acromegaly compared to the control group. The study group consisted of 104 patients with acromegaly and 64 healthy subjects constituting the control group. In the whole acromegaly group, the data reveal that the homozygous for risk allele carriers (rs1421085, rs9930506, rs9939609) as well as carriers of only one risk allele have lower IGF-1 concentrations. In the well-controlled acromegaly group, the homozygous for three risk allele carriers of FTO gene polymorphisms have lower HDL cholesterol concentration (rs1121980, rs1421085, rs993609). In the cured acromegaly group, homozygous risk allele carriers rs9930506 tend to have higher levels of total cholesterol and LDL cholesterol. These associations are not observed in the control group. Conclusion: there is an association between FTO gene polymorphisms and the metabolism of lipids, suggesting that the FTO gene may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1, implying that FTO gene may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.

Keywords: FTO; acromegaly; cardiovascular diseases; polymorphism.

MeSH terms

  • Acromegaly* / genetics
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO / genetics
  • Body Mass Index
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Insulin-Like Growth Factor I* / genetics
  • Obesity / complications
  • Obesity / genetics
  • Polymorphism, Single Nucleotide

Substances

  • Insulin-Like Growth Factor I
  • Alpha-Ketoglutarate-Dependent Dioxygenase FTO
  • FTO protein, human