title: The frequent 5,10-methylenetetrahydrofolate reductase C677T polymorphism is associated with a common haplotype in whites, Japanese, and Africans.
abstract: The common 5,10-methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism causes decreased activity of this enzyme and can be associated with mild-to-moderate hyperhomocysteinemia in homozygotes, particularly when there is folic acid deficiency, as well as with vascular dementia, arterial thrombosis, venous thrombosis, neural-tube defects, and fetal loss. When folic acid intake is sufficient, homozygotes for MTHFR 677T appear to be protected against colon cancer and acute lymphatic leukemia, and fetuses bearing this genotype have an augmented survival. The distribution of MTHFR 677T is worldwide, but its frequency in different populations varies extensively. In the present study, we addressed the question of whether the MTHFR 677T alteration has an ancestral origin or has occurred repeatedly. We analyzed the frequency distribution of the previously described polymorphism A1298C in exon 7 and of three intronic dimorphisms, in white Israelis (Jews and Arabs), Japanese, and Ghanaian Africans. The 677T allele was, remarkably, associated with one haplotype, G-T-A-C, in white and Japanese homozygotes. Among the Africans, analysis of maximum likelihood also disclosed an association with the G-T-A-C haplotype, although none of the 174 subjects examined was homozygous for MTHFR 677T. These results suggest that the MTHFR 677T alteration occurred on a founder haplotype that may have had a selective advantage.
authors.affiliation: Institute of Thrombosis and Hemostasis, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: Nurit
authors.initials: N
authors.lastname: Rosenberg
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Murata
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Ohene
authors.initials: O
authors.lastname: Opare-Sem
authors.forename: Ariella
authors.initials: A
authors.lastname: Zivelin
authors.forename: Eli
authors.initials: E
authors.lastname: Geffen
authors.forename: Uri
authors.initials: U
authors.lastname: Seligsohn
mesh_terms: D018912:Arabs / Q000235:genetics; D044466:Asian People / Q000235:genetics; D044383:Black People / Q000235:genetics; D005091:Exons / Q000235:genetics; D018703:Founder Effect; D005787:Gene Frequency; D005869:Ghana / Q000208:ethnology; D006239:Haplotypes / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D007438:Introns / Q000235:genetics; D007557:Israel / Q000208:ethnology; D007564:Japan / Q000208:ethnology; D007585:Jews / Q000235:genetics; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+); D008969:Molecular Sequence Data; D010088:Oxidoreductases / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D044469:Racial Groups / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D010088:Oxidoreductases; D045102:Methylenetetrahydrofolate Dehydrogenase (NAD+)