TRANSTHYRETIN SER-6 GENE-FREQUENCY IN INDIVIDUALS WITHOUT AMYLOIDOSIS

Transthyretin (TTR) Ser 6 was originally described in a Scottish kindr ed without amyloidosis. This variant, arising from a G --> A transitio n in codon 6 that destroys an MspI site and creates a BsrI site, was p resent in none of 50 controls, and was therefore throught 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 ot her TTR variants, raising the question whether it is actually a common polymorphism. To address this question, we performed PCR and restrict ion digestion of 574 DNA samples from people without evidence of amylo idosis or a known family history of amyloidosis. The TTR Ser 6 allele frequency was 33/558 (.060) in Caucasians (including 8/192 (.04) in No rth American Ashkenazic Jews, 16/218 (.07) in North American non-Jews, and 9/148 (.06) in Portuguese), 3(242 (.01) in African Americans, 0/1 40 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 va riant arose from a transition at a CG dinucleotide ''hot spot,'' it ma y have arisen on multiple occasions. These data indicate that TTR Ser 6 is a common non-amyloidogenic population polymorphism in Caucasians.