title: Common polymorphisms in methylenetetrahydrofolate reductase (MTHFR): relationships with plasma homocysteine concentrations and cognitive status in elderly northern italian subjects.
abstract: Hyperhomocysteinemia may be a risk factor for cognitive impairment. Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme in homocysteine (Hcy) metabolism. Both the MTHFR 677C-->T and the 1298A-->C polymorphisms are associated with mild hyperhomocysteinemia, particularly in conditions of low folate status. The prevalence of these MTHFR polymorphisms and their relationships with plasma total Hcy (tHcy), serum folate and cognitive function was evaluated in 194 elderly Italian individuals: 122 healthy controls (73.8 +/- 7.1 years of age), 24 cognitively- impaired- not-demented individuals (78.6 +/- 9.3 years), and 48 subjects with Alzheimer dementia (AD = 26), vascular dementia (VD =22; 85.5 +/- 7.0 years). Twenty-one percent of all subjects were homozygous for 677C-->T and 7 % for 1298A-->C polymorphism. No significant relationship was found betweenMTHFR polymorphisms and age, cognitive status and type of dementia. Plasma tHcy did not differ significantly by MTHFR genotypes, but, subjects of all genotypes with low serum folate (<12 nmole/l) had higher plasma tHcy (p < 0.001), than subjects with high serum folate (>= 12 nmole/l). The study suggests that 677C-->T and 1298A-->C polymorphisms are common in the Northern Italian population, but do not significantly affect plasma tHcy levels of elderly individuals, even under conditions of low folate status. The lack of association of age and cognitive function with MTHFR genotypes argues against a negative selection for these polymorphisms.
authors.affiliation: University of Bologna, Department of Internal Medicine, Cardioangiology, and Hepatology, University Hospital S. Orsola-Malpighi Via Massarenti 9, I - 40138 Bologna, Italy. ravaglia@med.unibo.it
authors.forename: G
authors.initials: G
authors.lastname: Ravaglia
authors.forename: P
authors.initials: P
authors.lastname: Forti
authors.forename: F
authors.initials: F
authors.lastname: Maioli
authors.forename: R C
authors.initials: RC
authors.lastname: Scali
authors.forename: G
authors.initials: G
authors.lastname: Arnone
authors.forename: T
authors.initials: T
authors.lastname: Talerico
authors.forename: T
authors.initials: T
authors.lastname: Pantieri
authors.forename: V
authors.initials: V
authors.lastname: Nativio
authors.forename: V
authors.initials: V
authors.lastname: Mantovani
authors.forename: M
authors.initials: M
authors.lastname: Bianchin
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002391:Catchment Area, Health; D003072:Cognition Disorders / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D005260:Female; D005492:Folic Acid / Q000097:blood; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D020138:Hyperhomocysteinemia / Q000097:blood* / Q000175:diagnosis / Q000453:epidemiology; D007558:Italy / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009483:Neuropsychological Tests; D017354:Point Mutation / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D015995:Prevalence; D012307:Risk Factors; D012720:Severity of Illness Index
chemical_list: D005492:Folic Acid; D042965:Methylenetetrahydrofolate Reductase (NADPH2)