RUOLO DEL POLIMORFISMO CA (19) DELLA REGIONE PROMOTER DEL GENE IGF-1 SULLA PRESENTAZIONE CLINICA DEI PAZIENTI ACROMEGALICI.

INTRODUCTION A highly polymorphic microsatellite, comprising a variable length of a Cytosine-Adenosine (CA) repeat sequence, has been identified in the promoter region of IGF-I gene. The number of CA repeats ranges between 10 and 24 and the most common allele in the Caucasian population contains 19 CA (192 bp) repeats. Several studies investigated the relationship between this polymorphism and IGF-I levels, with conflicting results. Aim of this study was to investigate the influence of this polymorphism on clinical and biochemical characteristics in 88 acromegalic patients. MATERIALS AND METHODS Different genotypes were studied by microsatellite method and patients were divided in 3 groups: group A, homozygous for 192 bp allele (n=26, 29.2%), group B, with a number of repeats ≥19 (n=36, 40%,) and group C, with a number of repeats ≤19 (n=27, 30%). 98 healthy patients were analyzed as controls. RESULTS No difference in the frequency of the different alleles was observed between patients and controls. In the acromegalic population the genotype did not influence IGF-I level at diagnosis. However, a worse of insulin sensitivity documented by a significant increase (p=0.01) in HOMA-IR was observed in group B (6.2±5.9) compared with group A (5.0±3.3) and C (4.0±3.1). Moreover, higher levels of total cholesterol and LDL (p=0.01 and p=0.01 respectively) were present in group B (233±49 and 168.5±46.6 respectively) compared to group C (175.3±43.4 and 104.0±38.2 respectively). Interestingly, the number of discrepant patients (high IGF-I and normal GH levels) during medical therapy was significantly higher in group B compared to groups A (p=0.02) and C (p=0.05). CONCLUSION Different IGF-I genotypes do not account for a different presentation in acromegalic patients. Nevertheless, our data suggest that a number of CA repeat higher than 19 may be related to a worse glucidic and lipidic metabolism and to a partial disease control during medical treatment.