Molecular Genetic Testing of Hemostasis and Thrombosis in Developing Countries: Achievements, Hopes, and Challenges

Margareth Castro Ozelo; Roman Zapata Esp.; Mohammad Qadura; Rouzbeh Chegeni; Maha Othman

doi:10.1055/s-0028-1103368

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2008; 34(6): 569-578
DOI: 10.1055/s-0028-1103368

Molecular Genetic Testing of Hemostasis and Thrombosis in Developing Countries: Achievements, Hopes, and Challenges

Margareth Castro Ozelo¹ , Roman Zapata Esp.² , Mohammad Qadura³ , Rouzbeh Chegeni⁴ , Maha Othman³

¹Hemocentro da UNICAMP, Campinas, Brazil
²Hospital Universitario San Vicente de Paúl Medellín, Antioquia, Colombia
³Department of Pathology and Molecular Medicine, Queen's University, Kingston, Canada
⁴Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

ABSTRACT

In today's developing world, how do we define a “developing country”? What level of effort and resources is invested in diagnosis, patient care, and research in those countries that we define to be developing? In particular, what is the situation with respect to molecular genetic testing in these countries? How much has been achieved to date, and what are the challenges to further achievements? This article describes the current status, challenges, and future hopes with respect to molecular genetic testing in hemostasis and thrombosis from the perspective of experts from three countries: Brazil, Colombia, and Iran. These individuals have lived and practiced genetic testing in their countries and have also had the experience to work and/or interact with the developed world to enable an appreciation of the difference.

KEYWORDS

Developing countries - genetic testing - hemostasis - thrombosis

Full Text

References

REFERENCES

1 Parra F C, Amado R C, Lambertucci J R, Rocha J, Antunes C M, Pena S DJ. Color and genomic ancestry in Brazilians. Proc Natl Acad Sci U S A. 2003; 100 177-182
2 Roisenberg I, Morton N E. Genetic aspects of hemophilias A and B in Rio Grande do Sul, Brazil. Hum Hered. 1971; 21 97-107
3 Camargo A A, Simpson A J. Collaborative research networks work. J Clin Invest. 2003; 112 468-471
4 Simpson A J, Reinach F C, Arruda P et al.. The genome sequence of the plant pathogen Xylella fastidiosa. The Xylella fastidiosa Consortium of the Organization for Nucleotide Sequencing and Analysis. Nature. 2000; 406 151-159
5 Arruda V R, Annichino-Bizzachi J M, Sonati M de F, Costa F F. Factor VIII and IX genes polymorphisms in a Brazilian black population. Thromb Haemost. 1993; 70 371
6 da Silva Júnior W A, Figueiredo M S. Analysis of factor VIII gene polymorphisms in Brazilian blacks reveals further differences in the black population. Hum Hered. 1994; 44 252-260
7 Figueiredo M S, Bowen D J, Silva Júnior W A, Zago M A. Factor IX gene haplotypes in Brazilian blacks and characterization of unusual DdeI alleles. Br J Haematol. 1994; 87 789-796
8 Figueiredo M S, Tavella M H, Simões B P. Large DNA inversions, deletions, and TaqI site mutations in severe haemophilia A. Hum Genet. 1994; 94 473-478
9 Arruda V R, Pieneman W C, Reitsma P H et al.. Eleven novel mutations in the factor VIII gene from Brazilian hemophilia A patients. Blood. 1995; 86 3015-3020
10 Soares R P, Chamone D A, Bydlowski S P. Factor VIII gene inversions and polymorphisms in Brazilian patients with haemophilia A: carrier detection and prenatal diagnosis. Haemophilia. 2001; 7 299-305
11 Figueiredo M S, Bowen D J, Silva Júnior W A, Zago M A. Factor IX gene haplotypes in Brazilian blacks and characterization of unusual DdeI alleles. Br J Haematol. 1994; 87 789-796
12 Manno C S, Pierce G F, Arruda V R et al.. AAV-mediated, liver-directed gene transfer for severe hemophilia B: successful transduction and limitations imposed by the host immune response. Nat Med. 2006; 12 342-347
13 Bertina R M, Koeleman B P, Koster T et al.. Mutation in blood coagulation factor V associated with resistance to activated protein C. Nature. 1994; 369 64-67
14 Arruda V R, Annichino-Bizzacchi J M, Costa F F, Reitsma P H, Factor V. Leiden (FVQ 506) is common in a Brazilian population. Am J Hematol. 1995; 49 242-243
15 Poort S R, Rosendaal F R, Reitsma P H, Bertina R M. A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis. Blood. 1996; 88 3698-3703
16 Arruda V R, Annichino-Bizzacchi J M, Gonçalves M S, Costa F F. Prevalence of the prothrombin gene variant (nt20210A) in venous thrombosis and arterial disease. Thromb Haemost. 1997; 78 1430-1433
17 Pieroni F, Lourenço D M, Morelli V M, Maffei F H, Zago M A, Franco R F. Cytokine gene variants and venous thrombotic risk in the BRATROS (Brazilian Thrombosis Study). Thromb Res. 2007; 120 221-229
18 Mello T B, Siqueira L H, Montavão S A, Ozello M C, Annichino-Bizzacchi J M. Low density lipoprotein receptor-related protein polymorphisms are not risk factors for venous thromboembolism. Thromb Res. 2008; 121 625-629
19 de Paula Sabino A, Guimarães D A, Ribeiro D D et al.. Increased factor V Leiden frequency is associated with venous thrombotic events among young Brazilian patients. J Thromb Thrombolysis. 2007; 24 261-266
20 Lourenço D M, Noguti M A, Juliano L. Antithrombin III dosage using the chromogenic substrate Tos-Gly-Pro-Arg-NAN, in several pathological situations. Rev Assoc Med Bras. 1995; 41 373-378
21 Pugliese L, Arruda V R, Annichino-Bizzacchi J M. A novel nonsense mutation 6, E - X in the protein S gene causes type I deficiency. Hum Hered. 1999; 49 121-122
22 Arnaldi L A, Polimeno N C, Arruda V R, Annichino-Bizzacchi J M. A novel splice site mutation in a Brazilian patient with hereditary antithrombin deficiency type I. Hum Hered. 1999; 49 119-120
23 Singh Y S, Arruda V R, Ozello M C, Machado T F, Annichino-Bizzacchi M M. Identification of one novel and three other point mutations in the protein C gene of five unrelated Brazilian patients with hereditary protein C deficiency. Haematologica. 2000; 85 891-893
24 Pan American Health Organization (PAHO) .Available at http://www.paho.org. Accessed August 7, 2008
25 Bedoya G, Montoya P, García J et al.. Admixture dynamics in Hispanics: a shift in the nuclear genetic ancestry of a South American population isolate. Proc Natl Acad Sci U S A. 2006; 103 7234-7239
26 Liascovich R, Rittler M, Castilla E. Consanguinity in South América: demographic aspects. Hum Hered. 2001; 51 27-34
27 Giraldo A. Genetic services in Colombia. Community Genet. 2004; 7 126-129
28 Kosik K S, Lopera F. Genetic testing must recognize impact of bad news on recipient. Nature. 2008; 454 158-159
29 Giraldo A, Gómez A, Salguero G et al.. MLH1 and MSH2 mutations in Colombian families with hereditary nonpolyposis colorectal cancer (Lynch syndrome)–description of four novel mutations. Fam Cancer. 2005; 4 285-290
30 Gómez A, Salguero G, García H et al.. Detection mutations in the DNA mismatch repair genes of hMLH1 and hMSH2 genes in Colombian families with suspicion of hereditary non-polyposis colorectal carcinoma (Lynch syndrome). Biomedica. 2005; 25 315-324
31 Heit J A, Thorland E C, Ketterling R P et al.. Germline mutations in Peruvian patients with hemophilia B: pattern of mutation in AmerIndians is similar to the putative endogenous germline pattern. Hum Mutat. 1998; 11 372-376
32 Heit J A, Ketterling R P, Zapata R E et al.. Brandenberg-type promoter mutation. Haemophilia. 1999; 5 73-75
33 Mulder K, Llinás A. The target joint. Haemophilia. 2004; 10(Suppl 4) 152-156
34 Llinás A. The role of synovectomy in the management of a target joint. Haemophilia. 2008; 14(Suppl 3) 177-180
35 Srivastava A, Rodeghiero F. Epidemiology of von Willebrand disease in developing countries. Semin Thromb Hemost. 2005; 31 569-576
36 SSC Working Group on Factor VIII and Factor IX .Rare bleeding disorders minutes from the XXI I STH Congress 2007. Available at http://www.rbdd.org/minute-july07.htm Accessed August 6, 2008
37 Rahimi Z, Vaisi-Raigani A, Nagel R L, Muniz A. Thrombophilic mutations among southern Iranian patients with sickle cell disease: high prevalence of factor V Leiden. J Thromb Thrombolysis. 2008; 25 288-292
38 Chegeni R, Kazemi B, Hajifathali A, Pourfathollah A A, Rastegar-Lari G. Factor V mutations in Iranian patients with activated protein C resistance and venous thrombosis. Thromb Res. 2007; 119 189-193
39 Florell S R, Rodgers G M. Inherited thrombotic disorders: an update. Am J Hematol. 1997; 54 53-60
40 Mannucci P M, Duga S, Peyvandi F. Recessively inherited coagulation disorders. Blood. 2004; 104 1243-1252
41 Peyvandi F, Duga S, Akhavan S, Mannucci P M. Rare coagulation deficiencies. Haemophilia. 2002; 8 308-321
42 Lak M, Peyvandi F, Mannucci P M. Clinical manifestations and complications of childbirth and replacement therapy in 385 Iranian patients with type 3 von willebrand disease. Br J Haematol. 2000; 111 1236-1239
43 Afrasiabi A, Artoni A, Karimi M, Peyvandi F, Ashouri E, Mannucci P M. Glanzmann thrombasthenia and Bernard-Soulier syndrome in south of Iran. Clin Lab Haematol. 2005; 27 324-327
44 Peyvandi F, Jayandharan G, Chandy M et al.. Genetic diagnosis of haemophilia and other inherited bleeding disorders. Haemophilia. 2006; 12(Suppl) 82-89
45 Peyvandi F. Carrier detection and prenatal diagnosis of hemophilia in developing countries. Semin Thromb Hemost. 2005; 31 544-554
46 Karimi M, Peyvandi F, Siboni S, Ardeshiri R, Gringeri A, Mannucci P M. Comparison of attitudes towards prenatal diagnosis and termination of pregnancy for haemophilia in Iran and Italy. Haemophilia. 2004; 10 367-369
47 Hedayat K M, Shooshtarizadeh P, Raza M. Therapeutic abortion in Islam: contemporary views of Muslim Shiite scholars and effect of recent Iranian legislation. J Med Ethics. 2006; 32 652-657

Maha OthmanM.D. Ph.D.

Department of Pathology and Molecular Medicine, Richardson Laboratory

Queen's University, Kingston, Ontario K7L 3N6, Canada

Email: Othman@queensu.ca