title: The evaluation of endothelin 1 (EDN1) and endothelin receptor type A (EDNRA) gene polymorphisms in Hashimoto's thyroiditis.
abstract: OBJECTIVE
  Endothelin1 (EDN1) is well established marker of inflammation. The functions of EDN1 are mediated mainly by endothelin receptors type A (EDNRA). The etiopathogenesis of Hashimoto's thyroiditis (HT) remains still elusive although the role of chronic inflammation and subsequent endothelial dysfunction has been established. This study examined firstly the possible association of EDN1 (G5665Tand T-1370G) and EDNRA (C+70G and G-231A) single nucleotide polymorphisms (SNPs) with the occurrence of HT, and evaluates the relationship between genotypes and clinical/laboratory manifestation of HT.
  
  
  METHODS
  We analyzed genotype and allele distributions of above mentioned polymorphisms in 163 patients with HT and 181 healthy controls by real-time PCR combined with melting curve analysis.
  
  
  RESULTS
  No significant associations between HT and variant alleles of EDN1 5665 and -1370, as well as EDNRA +70 and -231 SNPs were found. Haplotype analysis demonstrated that there was a strong (D'=0.76, r(2)=0.487) and weak (D'=0.403, r(2)=0.086) linkage disequilibrium (LD) between EDN1 -1370 and 5665, and between EDNRA -231 and +70 SNPs, respectively. However, haplotype frequencies in patients were similar to those in controls. In addition, it was observed that the EDNRA +70 G allele had protective effect against early (at age before 40 years) disease onset of HT (OR: 0.51, 95% CI=0.32-0.79, p=0.003).
  
  
  CONCLUSIONS
  Although no significant associations between susceptibility to HT with EDN1 5665 and -1370, as well as with EDNRA+70 and -231 SNPs were found, EDNRA +70 polymorphism was related with decreased risk for early onset HT.
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: A Fatih
authors.initials: AF
authors.lastname: Aydin
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey. Electronic address: pervinvural@yahoo.com.
authors.forename: Pervin
authors.initials: P
authors.lastname: Vural
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: Çoşkun Umut
authors.initials: ÇU
authors.lastname: Oruç
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: Semra
authors.initials: S
authors.lastname: Doğru-Abbasoğlu
authors.affiliation: Şişli Etfal Education and Research Hospital, II, Internal Medicine Clinic, Department of Endocrinology, Şişli, 34387 Istanbul, Turkey.
authors.forename: Ayşenur
authors.initials: A
authors.lastname: Özderya
authors.affiliation: Şişli Etfal Education and Research Hospital, II, Internal Medicine Clinic, Department of Endocrinology, Şişli, 34387 Istanbul, Turkey.
authors.forename: Berrin
authors.initials: B
authors.lastname: Karadağ
authors.affiliation: Istanbul University, Istanbul Faculty of Medicine, Department of Biochemistry, Istanbul, Turkey.
authors.forename: Müjdat
authors.initials: M
authors.lastname: Uysal
mesh_terms: D000328:Adult; D017668:Age of Onset; D004252:DNA Mutational Analysis; D019332:Endothelin-1 / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D050031:Hashimoto Disease / Q000453:epidemiology* / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044022:Receptor, Endothelin A / Q000235:genetics*; D012306:Risk; D014421:Turkey
chemical_list: D019332:Endothelin-1; D044022:Receptor, Endothelin A
keywords: Endothelin family; Hashimoto's thyroiditis; Inflammation; Polymorphism