Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

Abstract

ObjectiveThe aim of this study was to characterize the genetic variance of somatostatin receptor 5 (SSTR5) and investigate the possible correlation of such variants with acromegaly risk and different disease characteristics.Design and methodsThe SSTR5 gene coding region and 2000 bp upstream region was sequenced in 48 patients with acromegaly and 96 control subjects. Further, three single nucleotide polymorphisms (SNPs) were analyzed in the same group of acromegaly patients and in an additional group of 475 age- and sex-matched controls.ResultsIn total, 19 SNPs were identified in the SSTR5 gene locus by direct sequencing. Three SNPs (rs34037914, rs169068, and rs642249) were significantly associated with the presence of acromegaly using the initial controls. The allele frequencies were significantly (P<0.01) different between the acromegaly patients and the additional large control group. rs34037914 and rs642249 remained significantly associated with acromegaly after Bonferroni correction and permutation tests (odds ratio (OR)=3.38; 95% confidence interval (CI), 1.78–6.42; P=0.00016 and OR=2.41; 95% CI, 1.41–4.13; P=0.0014 respectively). Haplotype reconstruction revealed two possible risk haplotypes determined by rs34037914 (633T) and rs642249 (1044A) alleles. Both haplotypes were found in significantly higher frequency in acromegaly patients compared with controls (P<0.001). In addition, the 663T allele was significantly associated with a younger age of acromegaly diagnosis (unstandardized regression coefficient β=−10.4; P=0.002), increased body mass index (β=4.1; P=0.004), higher number of adenoma resection (P<0.001) and lack of observable tumor shrinkage after somatostatin analog treatment (P=0.014).ConclusionsOur results demonstrate a previously undetected strong association of two SSTR5 SNPs with acromegaly. The data also suggest a possible involvement of SSTR5 variants in decreased suppression of GH production and increased tumor proliferation.

Polymorphisms in MEN1 and DRD2 genes are associated with the occurrence and characteristics of pituitary adenomas

“…A similar association was observed for rs169068 (SSTR5), which is in LD with rs34037914. The OR in this study is within the 95% CI range of the previous study (2.63 (1.36-5.08) vs 4.51 (1.76-11.6)) (28). Nevertheless, in this study, we used a larger number of genotype markers resulting in a nonsignificant P-value after correction for 62 SNPs tested.…”

“…AIP mutations, normally associated with familial isolated PA, have also been shown to be rarely involved in the occurrence of sporadic cases (22,23) and lack of response to somatostatin analogs (SA) in acromegaly (18,23,24). Somatostatin acting through somatostatin receptors (SSTRs) is an important mediator of GH secretion and regulation of tumor proliferation; therefore, this system has been extensively studied in acromegaly (25,26,27), and our previous study identified an association between polymorphisms in SSTR5 with acromegaly and number of disease parameters (28). Similarly, the involvement of the dopamine system in clinically significant PA has been suggested, since dopamine agonists inhibit production of prolactin from the pituitary gland (29).…”

The lack of E318K MITF germline mutation in Latvian melanoma patients

“…The study was based on DNA samples and data from the Genome Database of Latvian Population (LGDB), a governmentfunded biobank (briefly described in Ciganoka et al (6) Centre were included in the study. Of these patients, 18 (3.8%) had a family history of melanoma, 11 (2.3%) had relatives with pancreatic cancer, 7 (1.5%) had multiple primary melanomas, and 49 (10.3%) were early-onset (age 35 y) melanoma patients.…”

Stronger Association of Common Variants in TCF7L2 Gene with Nonobese Type 2 Diabetes in the Latvian Population

“…From this group 1 093 subjects were randomly selected as controls maintaining the same gender proportion as in T2D cases. Genotyping was performed using matrix-assisted laser desorption/ionization (MALDI) time-of-fl ight (TOF) mass spectrometry (MS) for the rs7903146 as described previously [ 3 ] and TaqMan SNP genotyping assays on 7500 Real-Time PCR system in the case of rs7901695, rs11196205 and rs12255372 according to recommendation of manufacturer (Applied Biosystems, USA). Genotyping success rate was 99.1 %, 97.5 %, 99.1 % and 98.8 % for rs7901695, rs7903146, rs11196205 and rs12255372 respectively.…”

“…Case-control study groups were selected from the Latvian Genome Data Base (LGDB), a government funded biobank (shortly described in [ 3 ] ). SubPolymorphisms in the gene coding for transcription factor 7 like 2 (TCF7L2) are recognized as the strongest common genetic risk factors for type 2 diabetes (T2D) across multiple ethnicities.…”