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Association of IL-1 RN*2 allele and methionine synthase 2756 AA genotype with dementia severity of sporadic Alzheimer’s disease
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  1. P Bosco1,
  2. R-M Guéant-Rodríguez2,
  3. G Anello1,
  4. A Romano3,
  5. B Namour2,
  6. R S Spada1,
  7. F Caraci1,
  8. G Tringali4,
  9. R Ferri1,
  10. J-L Guéant2
  1. 1IRCCS Associazione Oasi Maria SS, Institute for Research on Mental Retardation and Brain Aging, Troina, Italy
  2. 2Cellular and Molecular Pathology in Nutrition, EMI–INSERM 0014, Vandoeuvre lès Nancy, France
  3. 3Department of Internal Medicine and Geriatrics, UCSC, CI Columbus, Rome, Italy
  4. 4Istituto Ricerca Medica ed Ambientale, Catania, Italy
  1. Correspondence to:
 Professor J L Guéant
 EMI–INSERM 0014, Faculty of Medicine, BP 184, 54500 Vandoeuvre lès Nancy, France; jean-louis.gueantmedecine.uhp-nancy.fr

Abstract

Background: Genetic polymorphisms of APO-E, homocysteine, and the IL-1 gene cluster (IL-1A, IL-1B, receptor antagonist IL-1RN) are associated with sporadic Alzheimer’s disease and may involve interdependent pathways of neuronal toxicity.

Objective: To determine whether these polymorphisms and the genetic determinants of homocysteine (methylenetetrahydrofolate reductase, MTHFR; methionine synthase, MTR; transcobalamin, TC) are associated with an increased risk of severe dementia in Alzheimer’s disease.

Methods: 152 patients with Alzheimer’s disease and 136 controls were studied. The association of occurrence and dementia severity (Reisberg score <6 and ⩾6) of Alzheimer’s disease with APO-E, IL-1A, IL-1B, IL-1RN, MTHFR677 C→T and 1298A→C, MTR 2756 A→G, and TC 776 C→G polymorphisms was evaluated by multivariate logistic regression analysis after adjustment for age, sex, and age of onset of Alzheimer’s disease.

Results:IL-1A TT and IL-1B CT/TT associated genotypes were at risk of Alzheimer’s disease (odds ratio 4.80 (95% confidence interval, 1.32 to 17.40), p = 0.017); the MTR 2756 AA genotype was at risk of severe dementia (OR 2.97 (1.23 to 7.21), p = 0.016); IL-1 RN*2 was protective (OR 0.28, (0.11 to 0.69), p = 0.006). Allele ϵ4 of the APO-E and IL-1B CC genotypes increased the risk of severe Alzheimer’s disease associated with the MTR 2756 AA genotype by 3.3-fold and 1.5-fold, respectively.

Conclusions: Distinct determinants of the IL-1 gene cluster are related to the generation and progression of Alzheimer’s disease. MTR only influences progression of the disease, which may be enhanced by carriage of allele ϵ4 of APO-E.

  • MTHFR, methylenetetrahydrofolate reductase
  • MTR, methionine synthase
  • TC, transcobalamin
  • Alzheimer’s disease
  • methionine synthase
  • IL-1 receptor antagonist
  • gene polymorphism

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Footnotes

  • Competing interests: none declared

  • P Bosco, R-M Guéant-Rodríguez, and G Anello contributed equally to this work