title: Prevalence of hyperhomocysteinemia in adult gluten-sensitive enteropathy at diagnosis: role of B12, folate, and genetics.
abstract: OBJECTIVE
  Hyperhomocysteinemia, a risk factor for thrombosis, recurrent miscarriages, and osteoporosis, might derive from acquired folate and vitamin B 12 deficiencies and from a C677T mutation in methylene-tetrahydrofolate reductase (MTHFR) gene. Undiagnosed gluten-sensitive enteropathy (GSE) is associated with vitamin deficiencies, osteoporosis, and recurrent miscarriages. We evaluated the prevalence and the risk factors for hyperhomocysteinemia in patients with newly diagnosed GSE.
  
  
  METHODS
  In this prospective study performed in a tertiary care setting, 40 consecutive subjects with newly diagnosed GSE were evaluated for homocysteine, folate, and vitamin B 12 levels and for C677T polymorphism. One hundred twenty sex- and age-matched healthy control subjects were studied. Nonparametric tests and multiple regression analysis were used to evaluate the risk factors in inducing hyperhomocysteinemia in the GSE population.
  
  
  RESULTS
  Hyperhomocysteinemia was more frequent in GSE patients than in control subjects (8/40, 20.0% vs 7/120, 5.8%) (relative risk, 3.4; 95% confidence interval, 1.3-8.9), as well as folate deficiency (17/40, 42.5% vs 10/120, 8.3%) (relative risk, 5.1; 95% confidence interval, 2.5-10.2). Multiple regression analysis showed that folate and B 12 levels were independently and inversely associated with homocysteine levels, whereas homozygosity for the MTHFR thermolabile variant was not. The prevalence of MTHFR variant in GSE population was not different from that reported in racially comparable control groups. Gluten-free diet was able to normalize folate, vitamin B 12 , and homocysteine levels.
  
  
  CONCLUSIONS
  Hyperhomocysteinemia is frequent in newly diagnosed GSE. Vitamin deficiencies caused by malabsorption are the most important determinants of this condition. Hyperhomocysteinemia might contribute to the occurrence of common complications of undiagnosed GSE.
authors.affiliation: Gastroenterology and Gastrointestinal Endoscopy Service, IRCCS Maggiore Hospital and University of Milan, Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Saibeni
authors.forename: Anna
authors.initials: A
authors.lastname: Lecchi
authors.forename: Gianmichele
authors.initials: G
authors.lastname: Meucci
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
authors.forename: Liliana
authors.initials: L
authors.lastname: Tagliabue
authors.forename: Emanuele
authors.initials: E
authors.lastname: Rondonotti
authors.forename: Sara
authors.initials: S
authors.lastname: Formenti
authors.forename: Roberto
authors.initials: R
authors.lastname: De Franchis
authors.forename: Maurizio
authors.initials: M
authors.lastname: Vecchi
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D002446:Celiac Disease / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D002851:Chromatography, High Pressure Liquid; D004247:DNA / Q000235:genetics*; D005260:Female; D005492:Folic Acid / Q000097:blood*; D005838:Genotype; D006710:Homocysteine / Q000097:blood; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood / Q000188:drug therapy / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000097:blood / Q000235:genetics*; D009154:Mutation; D015995:Prevalence; D011446:Prospective Studies; D011863:Radioimmunoassay; D012307:Risk Factors; D014805:Vitamin B 12 / Q000097:blood*
chemical_list: D015415:Biomarkers; D006710:Homocysteine; D004247:DNA; D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D014805:Vitamin B 12