Analysis of somatostatin receptors 2 and 5 polymorphisms in patients with acromegaly.
OBJECTIVE
The aim of the study was to investigate the possible correlation of single nucleotide polymorphisms in somatostatin receptor (SSTR)2 and SSTR5 genes with the responsiveness to somatostatin analogs in a cohort of acromegalic patients.


METHODS
Three single nucleotide polymorphisms (a-83 g, c-57 g, and t80c) of SSTR2 and three (t-461c, c325t, and c1004t) of SSTR5 were analyzed in 66 acromegalic patients with different responsiveness to somatostatin analogs and 66 healthy controls.


RESULTS
Allele frequencies in patients and controls were similar. No association between SSTR2 genotypes and GH and IGF-I levels was found. When considering SSTR5 variants, patients homozygous or heterozygous for the substitution c1004 (P+) showed basal IGF-I levels significantly lower than patients homozygous for 1004t (P-). Moreover, serum GH levels were lower in patients with P+/T- haplotype (having c1004 allele and no t-461 allele) than in those with P-/T+. No correlation between SSTR2 and SSTR5 genotypes, responsiveness to somatostatin therapy, and mRNA expression in the removed adenomas (n = 10) was found.


CONCLUSIONS
These data suggest a role for SSTR5 t-461c and c1004t alleles in influencing GH and IGF-I levels in patients with acromegaly, whereas SSTR2 and SSTR5 variants seem to have a minor role in determining the responsiveness to somatostatin analogs.
Filopanti
M
M
Institute of Endocrine Sciences, University of Milan, Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Istituto di Ricovero e Cura a Curattere Scientifico, Milan, Italy.
Ronchi
C
C
Ballarè
E
E
Bondioni
S
S
Lania
A G
AG
Losa
M
M
Gelmini
S
S
Peri
A
A
Orlando
C
C
Beck-Peccoz
P
P
Spada
A
A
D020121:5' Untranslated Regions / Q000235:genetics; D000172:Acromegaly / Q000188:drug therapy / Q000235:genetics*; D000328:Adult; D015331:Cohort Studies; D004351:Drug Resistance / Q000235:genetics; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000032:analysis; D017481:Receptors, Somatostatin / Q000235:genetics*; D013004:Somatostatin / Q000031:analogs & derivatives / Q000627:therapeutic use
D020121:5' Untranslated Regions; D012333:RNA, Messenger; D017481:Receptors, Somatostatin; D013004:Somatostatin; C094573:somatostatin receptor 5; C093733:somatostatin receptor 2