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Search: L773:1479 683X OR L773:0804 4643 > (2010-2014) > Identification of s...

  • Ciganoka, Darja (author)

Identification of somatostatin receptor type 5 gene polymorphisms associated with acromegaly

  • Article/chapterEnglish2011

Publisher, publication year, extent ...

  • 2011
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:uu-161575
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-161575URI
  • https://doi.org/10.1530/EJE-11-0416DOI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Objective: The 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 methods: The 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. Results: In 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 beta=-10.4; P=0.002), increased body mass index (beta=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). Conclusions: Our 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.

Added entries (persons, corporate bodies, meetings, titles ...)

  • Balcere, Inga (author)
  • Kapa, IvoUppsala universitet,Funktionell farmakologi (author)
  • Peculis, Raitis (author)
  • Valtere, Andra (author)
  • Nikitina-Zake, Liene (author)
  • Lase, Ieva (author)
  • Schiöth, Helgi B.Uppsala universitet,Funktionell farmakologi(Swepub:uu)helgschi (author)
  • Pirags, Valdis (author)
  • Klovins, JanisUppsala universitet,Funktionell farmakologi (author)
  • Uppsala universitetFunktionell farmakologi (creator_code:org_t)

Related titles

  • In:European Journal of Endocrinology165:4, s. 517-5250804-46431479-683X

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