GEOGRAPHICAL-DISTRIBUTION OF TTR MET(30) CARRIERS IN NORTHERN SWEDEN - DISCREPANCY BETWEEN CARRIER FREQUENCY AND PREVALENCE RATE

The first Swedish case of familial amyloidotic polyneuropathy (FAP) was published in 1965. The same transthyretin (TTR met(30)) mutation as that seen in Japanese, Portuguese, and other populations was also found in Swedish FAP patients. More than 350 patients with clinical manifestations of FAP have been diagnosed in northern Sweden, most of them originating from the areas around Skelleftea and Pitea. The mean age of onset is 56 years, much later than in patients from Japan and Portugal. To estimate the frequency of the TTR met(30) mutation in the counties of Vasterbotten and Norrbotten, sera from 1276 persons aged 24 to 65 years, randomly sampled from a health programme (MONICA), were screened with the monoclonal antibody FD6. In 19 persons, 13 females and six males, a positive reaction was seen in an Elisa test using this antibody. DNA analysis confirmed the TTR met(30) mutation and showed that 18 were heterozygous and one homozygous for this mutation. Other mutations were not looked for in this study. The mean TTR met(30) Carrier frequency in the area was 1.5% ranging from 0.0 to 8.3% in 23 subpopulations. There was a notable discrepancy between the regional distribution of the TTR met(30) allele and the morbidity rate for FAP. The estimated number of TTR met(30) gene carriers in a total population of 500 000 in the area is approximately 7500. The penetrance of the TTR met(30) mutation shows considerable variation between families, and the overall diagnostic (predictive) value in this population is as low as around 2%.