Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly
| Autor: | Helgi B. Schiöth, Ieva Lase, Janis Klovins, Raitis Peculis, Ivo Kapa, Andra Valtere, Inga Balcere, Liene Nikitina-Zake, Valdis Pirags, Darja Ciganoka |
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| Rok vydání: | 2011 |
| Předmět: |
Male
medicine.medical_specialty MEDICINE [Research Subject Categories] Endocrinology Diabetes and Metabolism Single-nucleotide polymorphism Biology Polymorphism Single Nucleotide Somatostatin receptor Endocrinology Internal medicine Acromegaly Databases Genetic medicine Humans Receptors Somatostatin Allele education Allele frequency Alleles Aged education.field_of_study Somatostatin receptor-5 Polymorphism Genetic Reverse Transcriptase Polymerase Chain Reaction Haplotype General Medicine Odds ratio DNA Middle Aged medicine.disease Latvia Hormones Treatment Outcome Haplotypes Clinical Study Female |
| Zdroj: | European Journal of Endocrinology |
| ISSN: | 1479-683X |
| Popis: | 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 (PP=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 (Pβ=−10.4; P=0.002), increased body mass index (β=4.1; P=0.004), higher number of adenoma resection (PP=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. |
| Databáze: | OpenAIRE |
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