title: An Association Study Between Gene Polymorphisms of Folic Acid Metabolism Enzymes and Biochemical and Hormonal Parameters in Acromegaly.
abstract: OBJECTIVE
  Folate metabolism is fundamental to several biological functions and required for cell replication, division, and survival. The mammalian folic acid cycle is highly complex and the enzymes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR), have crucial roles in this metabolic pathway. The common polymorphisms of the MTHFR (C677T and A1298C), MTRR (A66G), and MTR (A2756G) enzymes are well documented as folate deficiency-related disorders, but their roles have not been examined in acromegalic patients. The aim of this study was to compare the genotypic distribution of these gene polymorphisms between patients with acromegaly and controls and explore whether these polymorphisms were associated with biochemical and hormonal parameters in acromegaly. We examined 91 acromegaly patients and 112 healthy subjects who were compared in terms of age and gender. Blood specimens of the subjects were collected in tubes containing ethylenediaminetetraacetic acid. Genomic DNA was isolated from peripheral blood leukocytes and genotyping of the MTHFR (C677T and A1298C) gene polymorphisms was assessed by melting temperature analyses after real-time polymerase chain reaction (PCR), whereas MTRR A66G and MTR A2756G gene polymorphism analyses were performed by PCR/restriction fragment length polymorphism from the isolated DNA of the subjects.
  
  
  RESULTS
  MTHFR-677TT genotype frequency was significantly higher in the acromegaly group than the control group (p=0.017), and a significant increase was found in fibrinogen (p=0.032) levels in 677TT-carrying acromegaly patients. MTRR-66AA genotype was significantly higher in the control group than the acromegaly group (p=0.004). Total cholesterol (p=0.048) and C-reactive protein (p=0.046) levels decreased significantly in 66AA genotypes. Although MTR-2756AG genotype frequency was not different between the control and acromegaly groups, 2756AG genotype-carrying individuals have higher left carotid intima-media thickness levels within the patient group.
  
  
  CONCLUSIONS
  Our results suggest that polymorphisms of the genes encoding the folic acid metabolism enzymes affect biochemical parameters in acromegaly and this may result in predispositions to some complications associated with folate metabolism and acromegaly.
authors.affiliation: 1 Department of Medical Biology, Ege University Medicine Faculty , Izmir, Turkey .
authors.forename: Aslı
authors.initials: A
authors.lastname: Tetik Vardarlı
authors.affiliation: 2 Department of Endocrinology and Metabolism, Isparta State Hospital , Isparta, Turkey .
authors.forename: Ayhan
authors.initials: A
authors.lastname: Zengi
authors.affiliation: 1 Department of Medical Biology, Ege University Medicine Faculty , Izmir, Turkey .
authors.forename: Vildan
authors.initials: V
authors.lastname: Bozok Çetintaş
authors.affiliation: 3 Department of Endocrinology and Metabolism, Health Application and Research Center, Sifa University , Izmir, Turkey .
authors.forename: Muammer
authors.initials: M
authors.lastname: Karadeniz
authors.affiliation: 4 Department of Radio Diagnostic, Ege University Medical School , Izmir, Turkey .
authors.forename: Sadık
authors.initials: S
authors.lastname: Tamsel
authors.affiliation: 1 Department of Medical Biology, Ege University Medicine Faculty , Izmir, Turkey .
authors.forename: Ali Şahin
authors.initials: AŞ
authors.lastname: Küçükaslan
authors.affiliation: 5 Department of Biostatistic, Ege University Medical School , Izmir, Turkey .
authors.forename: Timur
authors.initials: T
authors.lastname: Köse
authors.affiliation: 6 Department of Endocrinology and Metabolism Disease, Ege University Medical School , Izmir, Turkey .
authors.forename: Füsun
authors.initials: F
authors.lastname: Saygılı
authors.affiliation: 1 Department of Medical Biology, Ege University Medicine Faculty , Izmir, Turkey .
authors.forename: Zuhal
authors.initials: Z
authors.lastname: Eroglu
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000172:Acromegaly / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D000328:Adult; D059168:Carotid Intima-Media Thickness; D016022:Case-Control Studies; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics*; D005492:Folic Acid / Q000235:genetics / Q000378:metabolism*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D060888:Real-Time Polymerase Chain Reaction; D012307:Risk Factors
chemical_list: D005492:Folic Acid; C111241:methionine synthase reductase; D005287:Ferredoxin-NADP Reductase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase