title: Transthyretin Ser 6 gene frequency in individuals without amyloidosis.
abstract: Transthyretin (TTR) Ser 6 was originally described in a Scottish kindred without amyloidosis. This variant, arising from a G-->A transition in codon 6 that destroys an MspI site and creates a BsrI site, was present in none of 50 controls, and was therefore thought to be rare. This variant has subsequently been found in a normal human cDNA liver library and in two unrelated patients with familial amyloidosis and other TTR variants, raising the question whether it is actually a common polymorphism. To address this question, we performed PCR and restriction digestion of 574 DNA samples from people without evidence of amyloidosis or a known family history of amyloidosis. The TTR Ser 6 allele frequency was 33/558 (.060) in Caucasians (including 8/192 (.04) in North American Ashkenazic Jews, 16/218 (.07) in North American non-Jews, and 9/148 (.06) in Portuguese), 3(242 (.01) in African Americans, 0/140 in Africans, and 0/208 in Asians. These data are most suggestive of a single Caucasian founder and the known 25% admixture of "Caucasian" genes in the African-American population. Alternatively, as this variant arose from a transition at a CG dinucleotide "hot spot," it may have arisen on multiple occasions. These data indicate that TTR Ser 6 is a common non-amyloidogenic population polymorphism in Caucasians.
authors.affiliation: Department of Medicine, New York University School of Medicine, NY.
authors.forename: D R
authors.initials: DR
authors.lastname: Jacobson
authors.forename: I L
authors.initials: IL
authors.lastname: Alves
authors.forename: M J
authors.initials: MJ
authors.lastname: Saraiva
authors.forename: S N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: J N
authors.initials: JN
authors.lastname: Buxbaum
mesh_terms: D000686:Amyloidosis / Q000235:genetics; D018703:Founder Effect; D005787:Gene Frequency; D005998:Glycine / Q000235:genetics; D006801:Humans; D017354:Point Mutation; D011110:Polymorphism, Genetic; D011228:Prealbumin / Q000235:genetics*; D012694:Serine / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D011228:Prealbumin; D012694:Serine; D005998:Glycine