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Previous Volume 340:1592-1593 May 20, 1999 Number 20 Next

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To the Editor: In their article on mutations of the cystic fibrosis gene in patients with chronic pancreatitis, Sharer et al. (Sept. 3 issue)¹ concluded that the frequency of carriers of the 5T allele was significantly higher in these patients than in the general population. However, we believe that this conclusion may be incorrect. The authors did not use for comparison the control group of 600 unrelated partners of persons with a family history of cystic fibrosis in the northwest of England.² Rather, they used the series studied by Kiesewetter et al.,³ which included persons from the United States, Northern Ireland, Italy, and Greece. The control group should represent the population from which the case patients were selected. Moreover, the carrier rate of 10.4 percent for the 5T allele found among 134 patients with chronic pancreatitis was compared with a 5 percent prevalence among 224 normal chromosomes (143 from the parents of patients with cystic fibrosis and 81 from the general population).³ The comparison of the carrier prevalence rate with the allele prevalence rate is inappropriate because the former is approximately two times as high, since a person has two homologous chromosomes. Thus, their conclusion that the frequency of the 5T allele among patients with chronic pancreatitis is "twice as high as expected" is incorrect. To date, there is no evidence that the 5T allele confers susceptibility to chronic pancreatitis.⁴

Núria Malats, M.D., Ph.D.
Francisco X. Real, M.D., Ph.D.
Institut Municipal d'Investigació Mèdica
E-08003 Barcelona, Spain

References

1. Sharer N, Schwarz M, Malone G, et al. Mutations of the cystic fibrosis gene in patients with chronic pancreatitis. N Engl J Med 1998;339:645-652. [Free Full Text]
2. Super M, Schwarz MJ, Malone G, Roberts T, Haworth A, Dermody G. Active cascade testing for carriers of cystic fibrosis gene. BMJ 1994;308:1462-1467. [Free Full Text]
3. Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 1993;5:274-278. [CrossRef][Medline]
4. Cohn JA, Friedman KJ, Noone PG, Knowles MR, Silverman LM, Jowell PS. Relation between mutations of the cystic fibrosis gene and idiopathic pancreatitis. N Engl J Med 1998;339:653-658. [Free Full Text]

To the Editor: The length of the thymidine-repeat sequence in intron 8 of the cystic fibrosis gene (the polyT sequence) may be five, seven, or nine bases. The frequency with which these three alleles occur in a white population does not differ among studies,^1,2,3,4 with values of 5, 84, and 11 percent, respectively, being reported in the 224 normal chromosomes analyzed by Kiesewetter et al.¹ In our study of mutations of the cystic fibrosis gene in patients with chronic pancreatitis, we assumed that these figures would apply equally to the population in the northwest of England.

A total of 10.4 percent of the 134 patients with chronic pancreatitis whom we studied carried the 5T allele. We are grateful to Drs. Malats and Real for bringing to our attention that we incorrectly compared this carrier rate with a 5T allele frequency rate in the population of 5 percent. We acknowledge our error. In our conclusions, we should have stated that mutations of the CFTR gene — but not the 5T genotype — are associated with chronic pancreatitis. We agree that, unlike the case with congenital absence of the vas deferens⁴ and disseminated bronchiectasis,² a relation between susceptibility to chronic pancreatitis and the presence of a 5T allele remains unproved. This point exemplifies the differences among these three cystic fibrosis syndromes⁵ and the as yet undefined interactions between genotype and environmental factors in their causation.

Nicholas M. Sharer, M.R.C.P.
Poole Hospital NHS Trust
Dorset BH15 2JB, United Kingdom

Martin J. Schwartz, Ph.D.
Royal Manchester Children's Hospital
Manchester M27 4HA, United Kingdom

References

1. Kiesewetter S, Macek M Jr, Davis C, et al. A mutation in CFTR produces different phenotypes depending on chromosomal background. Nat Genet 1993;5:274-278.
2. Pignatti PF, Bombieri C, Benetazzo M, et al. CFTR gene variant IVS8-5T in disseminated bronchiectasis. Am J Hum Genet 1996;58:889-892. [Medline]
3. Friedman KJ, Heim RA, Knowles MR, Silverman LM. Rapid characterization of the variable length polythymidine tract in the cystic fibrosis (CFTR) gene: association of the 5T allele with selected CFTR mutations and its incidence in atypical sinopulmonary disease. Hum Mutat 1997;10:108-115. [CrossRef][Medline]
4. Chillón M, Casals T, Mercier B, et al. Mutations in the cystic fibrosis gene in patients with congenital absence of the vas deferens. N Engl J Med 1995;332:1475-1480. [Free Full Text]
5. Sharer NM, Schwartz M. Mutations of the cystic fibrosis gene and pancreatitis. N Engl J Med 1999;340:238-239. [Free Full Text]

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This article has been cited by other articles:

• Malats, N, Casals, T, Porta, M, Guarner, L, Estivill, X, Real, F X (2001). Cystic fibrosis transmembrane regulator (CFTR) Delta F508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. Gut 48: 70-74 [Abstract] [Full Text]