Endocrine Abstracts

Acromegaly is characterized by two-fold higher mortality than in the general population. The leading causes of morbidity and mortality in patients with acromegaly are cardiovascular diseases (CVD). Many population-based studies suggest a role of genetic background in CVD and associated metabolic disturbances. In 2007, FTO (fat mass and obesity associated) gene polymorphisms were discovered. According to a few studies, the polymorphisms of FTO gene are associated with obesity, as well as with an increased risk of CVD. It has been suggested that the GH / IGF-1 axis may be the mediator of the relationship between the FTO gene and BMI. The aim of our study was to determine the relationship of four risk alleles of selected FTO gene polymorphisms: rs1121980 (allele T), rs1421085 (allele C), rs9930506 (allele G), rs9939609 (allele A) with: selected parameters of lipid metabolism and IGF-1 and GH levels in the group of patients with acromegaly compared to control group. We showed that the distribution of the risk-alleles of the analyzed genotypes did not deviate between acromegaly and control group. The data revealed that homozygotes for risk allele carriers as well as only carrier of risk allele have lower IGF-1 (IGF-1 x ULN) concentrations. We did not find any association of FTO gene polymorphisms with lipid metabolism in the whole acromegalic group but found these when we analyzed acromegalic patients according to the activity of the disease. In controlled acromegaly group we showed that homozygotes for three risk alleles had lower HDL cholesterol concentration. Homozygotes for the rs1121980-risk allele (allele T) had lower HDL cholesterol concentration than carriers of the CC and CT genotypes (P×=×0.037). Homozygotes for the rs1421085-risk allele (allele C) had lower HDL cholesterol concentration than carriers of the TT and CT genotypes (P×=×0.035). Homozygotes for rs993609–risk allele (allele A) had lower HDL concertation than carriers of AT and TT genotypes (P=0.09). We observed a similar situation for total cholesterol and LDL cholesterol. What is important to note, we did not observe this association in the control group. Conclusion: There is an association between FTO gene polymorphisms and lipids metabolism suggesting FTO gene polymorphisms may be associated with higher CVD risk in patients with acromegaly. In addition, there is an association between FTO gene polymorphisms and IGF-1 concertation implying FTO gene polymorphisms may influence/modify IGF-1 synthesis. Further investigation on a larger scale is required to provide more precise evidence.