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Differences in Expression of Cystic Fibrosis in Blacks and Whites

Differences in Expression of Cystic Fibrosis in Blacks and Whites Abstract • The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three—basepair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein, accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations. (AJDC. 1991;145:94-97) References 1. Knowlton RG, Cohen-Haguenauer 0, Van Cong N, et al. A polymorphic DNA marker linked to cystic fibrosis located on chromosome 7 . Nature . 1985;318:380-382.Crossref 2. Wainwright BJ, Scambler PJ, Schmidtke J, et al. Localization of cystic fibrosis locus to human chromosome 7cen-q22 . Nature . 1985;318:384-385.Crossref 3. White R, Woodward S, Leppert M, et al. A closely linked genetic marker for cystic fibrosis . Nature . 1985;318:382-384.Crossref 4. Estivill X, Scambler PJ, Wainwright BJ, et al. Patterns of polymorphism and linkage disequilibrium for cystic fibrosis . Genomics . 1987;1: 254-263.Crossref 5. Cutting GR, Antonarakis SE, Buetow KH, Kasch LM, Rosenstein BJ, Kazazian HH. Analysis of DNA polymorphism haplotypes linked to the cystic fibrosis locus in North American black and caucasian families support the existence of multiple mutations of the cystic fibrosis gene . Am J Hum Genet . 1989;44:307-318. 6. Rommens JM, Ianuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking andjumping . Science . 1989;245:1059-1065.Crossref 7. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA . Science . 1989;245:1066-1073.Crossref 8. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis . Science . 1989;245:1073-1080.Crossref 9. Lemna WK, Feldman GL, Kerem B, et al. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis . N Engl J Med . 1990;322:291-296.Crossref 10. Cutting GR, Kasch LM, Rosenstein BJ, et al. A cluster of cystic fibrosis mutations in the first nucleotide binding domain of the cystic fibrosis conductance regulator protein . Nature . 1990;346:366-369.Crossref 11. Senecal JJ, Toury M, Camain R. Deux cas de fibrose cystique du pancreas chez l'enfant Africain realisant le syndrome de kwashiorkor . Bull Med Afr Occidentale Fr . 1954;11:95-99. 12. Kulczycki LL, Schauf V. Cystic fibrosis in blacks in Washington, D.C. AJDC . 1974;127:64-67. 13. Kulczycki LL, Guin GH, Mann N. Cystic fibrosis in negro children: results of a search . Clin Pediatr . 1964;3:692-705.Crossref 14. Stern RC, Doershuk CF, Boat TF, Tucker AS, Primiano FP, Matthews LW. Course of cystic fibrosis in black patients . J Pediatr . 1976;89: 412-417.Crossref 15. Heffer ET. Cystic fibrosis in black children . J Pediatr . 1977;90:324-325.Crossref 16. Kulczycki LL. Cystic fibrosis in black children revisited . J Pediatr . 1978;92:855.Crossref 17. Polgar G, Promadhat V. Pulmonary Function Testing in Children: Techniques and Standards . Philadelphia, Pa: WB Saunders Co; 1971. 18. Hsu KHK, Jenkins DE, Hsi BP, et al. Ventilatory functions of normal children and young adults: Mexican-American, white, and black, I: spirometry . J Pediatr . 1979;95:14-23.Crossref 19. Brasfield D, Hicks G, Soong S, Tiller R. The chest roentgenogram in cystic fibrosis: a new scoring system . Pediatrics . 1979;63:24-29. 20. Cox RR, Oakes D. Analysis of Survival Data . London, England: Chapman & Hall; 1984. 21. Nadler HL, Ben-Yoseph Y. Genetics . In: Taussig LM, ed. Cystic Fibrosis . New York, NY: Thieme-Stratton Inc; 1984:10-11. 22. Hammond KB, Reardon MC, Accurso FJ, et al. Early detection and follow-up of cystic fibrosis in newborns: the Colorado experience . In: Carter T, Willy AM, eds. Genetic Disease: Screening and Management . New York, NY: Alan R Liss Inc; 1986:81-101. 23. Wilcken B, Brown ARD, Urwin R, Brown DA. Cystic fibrosis screening by dried blood spot trypsin assay: results in 75,000 newborn infants . J Pediatr . 1983;102:383-387.Crossref 24. Allan JL, Robbie M, Phelan PD, Danks DM. The incidence and presentation of cystic fibrosis in Victoria 1955-1978 . Aust Paediatr J . 1980;16: 270-273. 25. Patient Registry . Rockville, Md: Cystic Fibrosis Foundation; 1987. 26. Prapphal N, Fitzpatrick SB, Getson P, Fink R, O'Donnell R, Chaney M. Cystic fibrosis in blacks in Washington, D.C.: fifteen years experience . J Natl Med Assoc . 1989;81:263-267. 27. Rosenstein BJ, Perman JA, Kramer SS. Peptic ulcer disease in cystic fibrosis: an unusual occurrence in black adolescents . AJDC . 1986; 140:966-969. 28. Sutz SA, Schlesinger ER, Feldman JG, et al. The epidemiology of peptic ulcer in childhood . Am J Public Health . 1970;60:492-498.Crossref 29. Miranti JP. A review of experience with peptic ulcer in adolescents and young adults in a university health service . J Am Coll Health . 1970;18:381. 30. Robb JDA, Thomas PS, Orszulok J, Odling-Smee GW. Duodenal ulcer in children . Arch Dis Child . 1972;47:688-696.Crossref 31. Eggleston PA, Rosenstein BJ, Stackhouse CM, Alexander MF. Airway hyperreactivity in cystic fibrosis . Chest . 1988;94:360-365.Crossref 32. Wood RE. Prognosis . In: Taussig LM, ed. Cystic Fibrosis . New York, NY: Thieme-Stratton Inc; 1984:434-460. 33. Kulczycki LL, Murphy TM, Bellanti JA. Pseudomonas colonization in cystic fibrosis . JAMA . 1978;240:30-34.Crossref 34. Wilmott RW, Tyson SL, Matthew DJ. Cystic fibrosis survival rates . AJDC . 1985;139:669-671. 35. Katz JN, Horowitz RI, Dolan TF, Shapiro ED. Clinical features as predictors of functional status in children with cystic fibrosis . J Pediatr . 1986;108:352-358.Crossref 36. Gaskin K, Gurwitz D, Durie P, Levison H, Forstner G. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption . J Pediatr . 1982;100:857-862.Crossref 37. Kraemer R, Hadorn B, Ross E. Classification at time of diagnosis and subsequent survival in patients with cystic fibrosis . Helv Paediatr Acta . 1977;32:107-114. 38. Hudson I, Phelan PD. Are sex, age at diagnosis, or mode of presentation prognostic predictors for cystic fibrosis? Pediatr Pulmonol . 1987;3:288-297.Crossref 39. Orenstein DM, Boat TF, Stern RC, et al. The effect of early diagnosis and treatment in cystic fibrosis . AJDC . 1977;131:973-975. 40. Gurwitz D, Corey M, Francis PW, Crozier D, Levison H. Perspectives in cystic fibrosis . Pediatr Clin North Am . 1979;26:603-615. 41. Estivill X, del Rio E, Casals T, Volpini V, Bazet M. Linkage disequilibrium for cystic fibrosis in Spanish families . Pediatr Pulmonol . 1988; S.2:96. Abstract. 42. Witt M, Erickson RP, Sing CF, Howatt WF, Farquhar S. The relationship of XV2c, KM19 and J3.11 haplotypes to clinical heterogeneity of cystic fibrosis . Pediatr Pulmonol . 1988;S.2:98. Abstract. 43. Kerem B, Buchanan JA, Durie P, et al. DNA marker haplotype association with pancreatic sufficiency in cystic fibrosis . Am J Hum Genet . 1989;44:827-834. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Diseases of Children American Medical Association

Differences in Expression of Cystic Fibrosis in Blacks and Whites

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Publisher
American Medical Association
Copyright
Copyright © 1991 American Medical Association. All Rights Reserved.
ISSN
0002-922X
DOI
10.1001/archpedi.1991.02160010100025
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Abstract

Abstract • The recent identification of the cystic fibrosis (CF) gene confirms that genetic heterogeneity occurs in CF. A three—basepair deletion in exon 10 resulting in a loss of the phenylalanine residue at amino acid position 508 of the gene product, termed the CF conductance regulator protein, accounts for 70% of cases of CF in white subjects. However, this gene defect occurs in only 37% of affected blacks. Analysis of CF genes from American blacks has revealed a number of mutations, most of which are unique to that population. We therefore searched for potential differences in expression of CF between 24 black and 48 white patients with CF matched for birth date and gender. Black patients more frequently presented with only respiratory symptoms (38% vs 10%). Black patients had fewer hospitalizations for pulmonary exacerbations (2 vs 6.9), a better mean forced vital capacity (77% vs 62% of predicted), and higher chest roentgenogram scores (18.2 vs 14.4) than white patients. Complication rates were similar except for a higher incidence of hyponatremic dehydration (21% vs 2%) and peptic ulcer disease (13% vs 0%) in blacks. Survival time appeared to be longer in blacks, but the difference was not statistically significant. We conclude that phenotypic differences exist between black and white patients with CF, which may be due to the genetic heterogeneity between these two populations. (AJDC. 1991;145:94-97) References 1. Knowlton RG, Cohen-Haguenauer 0, Van Cong N, et al. A polymorphic DNA marker linked to cystic fibrosis located on chromosome 7 . Nature . 1985;318:380-382.Crossref 2. Wainwright BJ, Scambler PJ, Schmidtke J, et al. Localization of cystic fibrosis locus to human chromosome 7cen-q22 . Nature . 1985;318:384-385.Crossref 3. White R, Woodward S, Leppert M, et al. A closely linked genetic marker for cystic fibrosis . Nature . 1985;318:382-384.Crossref 4. Estivill X, Scambler PJ, Wainwright BJ, et al. Patterns of polymorphism and linkage disequilibrium for cystic fibrosis . Genomics . 1987;1: 254-263.Crossref 5. Cutting GR, Antonarakis SE, Buetow KH, Kasch LM, Rosenstein BJ, Kazazian HH. Analysis of DNA polymorphism haplotypes linked to the cystic fibrosis locus in North American black and caucasian families support the existence of multiple mutations of the cystic fibrosis gene . Am J Hum Genet . 1989;44:307-318. 6. Rommens JM, Ianuzzi MC, Kerem B, et al. Identification of the cystic fibrosis gene: chromosome walking andjumping . Science . 1989;245:1059-1065.Crossref 7. Riordan JR, Rommens JM, Kerem B, et al. Identification of the cystic fibrosis gene: cloning and characterization of complementary DNA . Science . 1989;245:1066-1073.Crossref 8. Kerem B, Rommens JM, Buchanan JA, et al. Identification of the cystic fibrosis gene: genetic analysis . Science . 1989;245:1073-1080.Crossref 9. Lemna WK, Feldman GL, Kerem B, et al. Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis . N Engl J Med . 1990;322:291-296.Crossref 10. Cutting GR, Kasch LM, Rosenstein BJ, et al. A cluster of cystic fibrosis mutations in the first nucleotide binding domain of the cystic fibrosis conductance regulator protein . Nature . 1990;346:366-369.Crossref 11. Senecal JJ, Toury M, Camain R. Deux cas de fibrose cystique du pancreas chez l'enfant Africain realisant le syndrome de kwashiorkor . Bull Med Afr Occidentale Fr . 1954;11:95-99. 12. Kulczycki LL, Schauf V. Cystic fibrosis in blacks in Washington, D.C. AJDC . 1974;127:64-67. 13. Kulczycki LL, Guin GH, Mann N. Cystic fibrosis in negro children: results of a search . Clin Pediatr . 1964;3:692-705.Crossref 14. Stern RC, Doershuk CF, Boat TF, Tucker AS, Primiano FP, Matthews LW. Course of cystic fibrosis in black patients . J Pediatr . 1976;89: 412-417.Crossref 15. Heffer ET. Cystic fibrosis in black children . J Pediatr . 1977;90:324-325.Crossref 16. Kulczycki LL. Cystic fibrosis in black children revisited . J Pediatr . 1978;92:855.Crossref 17. Polgar G, Promadhat V. Pulmonary Function Testing in Children: Techniques and Standards . Philadelphia, Pa: WB Saunders Co; 1971. 18. Hsu KHK, Jenkins DE, Hsi BP, et al. Ventilatory functions of normal children and young adults: Mexican-American, white, and black, I: spirometry . J Pediatr . 1979;95:14-23.Crossref 19. Brasfield D, Hicks G, Soong S, Tiller R. The chest roentgenogram in cystic fibrosis: a new scoring system . Pediatrics . 1979;63:24-29. 20. Cox RR, Oakes D. Analysis of Survival Data . London, England: Chapman & Hall; 1984. 21. Nadler HL, Ben-Yoseph Y. Genetics . In: Taussig LM, ed. Cystic Fibrosis . New York, NY: Thieme-Stratton Inc; 1984:10-11. 22. Hammond KB, Reardon MC, Accurso FJ, et al. Early detection and follow-up of cystic fibrosis in newborns: the Colorado experience . In: Carter T, Willy AM, eds. Genetic Disease: Screening and Management . New York, NY: Alan R Liss Inc; 1986:81-101. 23. Wilcken B, Brown ARD, Urwin R, Brown DA. Cystic fibrosis screening by dried blood spot trypsin assay: results in 75,000 newborn infants . J Pediatr . 1983;102:383-387.Crossref 24. Allan JL, Robbie M, Phelan PD, Danks DM. The incidence and presentation of cystic fibrosis in Victoria 1955-1978 . Aust Paediatr J . 1980;16: 270-273. 25. Patient Registry . Rockville, Md: Cystic Fibrosis Foundation; 1987. 26. Prapphal N, Fitzpatrick SB, Getson P, Fink R, O'Donnell R, Chaney M. Cystic fibrosis in blacks in Washington, D.C.: fifteen years experience . J Natl Med Assoc . 1989;81:263-267. 27. Rosenstein BJ, Perman JA, Kramer SS. Peptic ulcer disease in cystic fibrosis: an unusual occurrence in black adolescents . AJDC . 1986; 140:966-969. 28. Sutz SA, Schlesinger ER, Feldman JG, et al. The epidemiology of peptic ulcer in childhood . Am J Public Health . 1970;60:492-498.Crossref 29. Miranti JP. A review of experience with peptic ulcer in adolescents and young adults in a university health service . J Am Coll Health . 1970;18:381. 30. Robb JDA, Thomas PS, Orszulok J, Odling-Smee GW. Duodenal ulcer in children . Arch Dis Child . 1972;47:688-696.Crossref 31. Eggleston PA, Rosenstein BJ, Stackhouse CM, Alexander MF. Airway hyperreactivity in cystic fibrosis . Chest . 1988;94:360-365.Crossref 32. Wood RE. Prognosis . In: Taussig LM, ed. Cystic Fibrosis . New York, NY: Thieme-Stratton Inc; 1984:434-460. 33. Kulczycki LL, Murphy TM, Bellanti JA. Pseudomonas colonization in cystic fibrosis . JAMA . 1978;240:30-34.Crossref 34. Wilmott RW, Tyson SL, Matthew DJ. Cystic fibrosis survival rates . AJDC . 1985;139:669-671. 35. Katz JN, Horowitz RI, Dolan TF, Shapiro ED. Clinical features as predictors of functional status in children with cystic fibrosis . J Pediatr . 1986;108:352-358.Crossref 36. Gaskin K, Gurwitz D, Durie P, Levison H, Forstner G. Improved respiratory prognosis in patients with cystic fibrosis with normal fat absorption . J Pediatr . 1982;100:857-862.Crossref 37. Kraemer R, Hadorn B, Ross E. Classification at time of diagnosis and subsequent survival in patients with cystic fibrosis . Helv Paediatr Acta . 1977;32:107-114. 38. Hudson I, Phelan PD. Are sex, age at diagnosis, or mode of presentation prognostic predictors for cystic fibrosis? Pediatr Pulmonol . 1987;3:288-297.Crossref 39. Orenstein DM, Boat TF, Stern RC, et al. The effect of early diagnosis and treatment in cystic fibrosis . AJDC . 1977;131:973-975. 40. Gurwitz D, Corey M, Francis PW, Crozier D, Levison H. Perspectives in cystic fibrosis . Pediatr Clin North Am . 1979;26:603-615. 41. Estivill X, del Rio E, Casals T, Volpini V, Bazet M. Linkage disequilibrium for cystic fibrosis in Spanish families . Pediatr Pulmonol . 1988; S.2:96. Abstract. 42. Witt M, Erickson RP, Sing CF, Howatt WF, Farquhar S. The relationship of XV2c, KM19 and J3.11 haplotypes to clinical heterogeneity of cystic fibrosis . Pediatr Pulmonol . 1988;S.2:98. Abstract. 43. Kerem B, Buchanan JA, Durie P, et al. DNA marker haplotype association with pancreatic sufficiency in cystic fibrosis . Am J Hum Genet . 1989;44:827-834.

Journal

American Journal of Diseases of ChildrenAmerican Medical Association

Published: Jan 1, 1991

References