title: Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease.
abstract: Endothelial Nitric Oxide Synthase (eNOS) is crucial for vascular homeostasis. Polymorphisms T786C and G894T affect eNOS regulation and have been related to various diseases. Sickle Cell Disease (SCD), a clinically diverse chronic hemolytic anemia, implies impaired nitric oxide bioavailability. Our aim was to determine eNOS genotype for T786C and G894T polymorphisms in Greek patients with SCD and to elucidate its consequences and effects if any on clinical phenotype. Seventy nine steady state cases, mostly compound heterozygous for Sickle Cell anemia/beta thalassemia and 48 controls were measured. Peripheral blood DNA was extracted and genotyped with PCR-RFLPs and Sanger sequencing. Total RNA was extracted from 18 patients and 9 controls and eNOS mRNA levels were determined by real-time PCR. Genotypes, allele distribution and eNOS mRNA levels did not differ between patients and controls, or among patients with different beta globin gene mutations. The 786CC genotype was more common in S/S and β0/S patients with retinopathy. Moreover, 894TT S/S and β0/S patients tended to have a higher hematocrit than 894GG and GT ones. However, the T786C eNOS genotype does not seem to affect peripheral blood cell-derived eNOS mRNA levels, at least in steady state conditions. This work is the first one describing the effects of eNOS polymorphisms on different forms of SCD, the first enrolling SCD patients of Caucasian origin and the first determining eNOS mRNA levels in peripheral blood from steady-state SCD patients.
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece. Electronic address: iakovosarm@hotmail.com.
authors.forename: Iakovos
authors.initials: I
authors.lastname: Armenis
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece.
authors.forename: Vassiliki
authors.initials: V
authors.lastname: Kalotychou
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece; Metropolitan Hospital, Athens, Greece.
authors.forename: Revekka
authors.initials: R
authors.lastname: Tzanetea
authors.affiliation: Department of Biology, NKUA, Athens, Greece.
authors.forename: Panagoula
authors.initials: P
authors.lastname: Kollia
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece; Department of Biology, NKUA, Athens, Greece.
authors.forename: Zoi
authors.initials: Z
authors.lastname: Kontogeorgiou
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece; Department of Biology, NKUA, Athens, Greece.
authors.forename: Dimitra
authors.initials: D
authors.lastname: Anastasopoulou
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece.
authors.forename: Marina
authors.initials: M
authors.lastname: Mantzourani
authors.affiliation: 1st Department of Internal Medicine, "Laiko" Hospital, NKUA, Medical School, Athens, Greece.
authors.forename: Michael
authors.initials: M
authors.lastname: Samarkos
authors.affiliation: Department of Pharmacology, NKUA, Medical School, Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Pantos
authors.affiliation: Department of Hematology, "Laiko" General Hospital, NKUA, Medical School, Athens, Greece.
authors.forename: Kostas
authors.initials: K
authors.lastname: Konstantopoulos
authors.affiliation: Metropolitan Hospital, Athens, Greece.
authors.forename: Ioannis
authors.initials: I
authors.lastname: Rombos
mesh_terms: D000328:Adult; D000368:Aged; D000755:Anemia, Sickle Cell / Q000150:complications / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D005260:Female; D006400:Hematocrit; D006454:Hemoglobins / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D052250:Nitric Oxide Synthase Type III / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D012164:Retinal Diseases / Q000208:ethnology / Q000209:etiology; D044465:White People
chemical_list: D006454:Hemoglobins; D012333:RNA, Messenger; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
keywords: Endothelial Nitric Oxide Synthase (eNOS); G894T; Hemoglobinopathies; Nitric oxide; Polymorphisms; Sickle cell disease; T786C