Skip to main content
Log in

Prevalence of MTHFR C677T Single Nucleotide Polymorphism in Genetically Isolated Populations in Jordan

  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Methylenetetrahydrofolate reductase (MTHFR) C677T single nucleotide polymorphism is a major inherited risk factor of venous thromboembolism. We sought to determine its prevalence in genetically isolated populations of Chechens and Circassians in Jordan. The MTHFR C677T mutation was analyzed from blood samples taken from 120 random unrelated Chechens and 72 Circassians. The prevalence of the MTHFR mutation in the Chechen population was 27.5% (allele frequency 15%); the prevalence among the Circassians was 50% (allele frequency 29.2%). The prevalence in the Chechen population is similar to that in Jordan and other world populations, but it is higher in the Circassian population. This study will contribute to understanding the interaction between genetic and environmental risk factors underlying thrombosis and will be useful in deciding which genetic variants should be tested in a clinical genetic testing service.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Antoniadi T, Hatzis T, Kroupis C, Economou-Petersen E, Petersen MB (1999) Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in a Greek population of blood donors. Am J Hematol 61(4):265–267

    Article  PubMed  CAS  Google Scholar 

  • Arnesen E, Refsum H, Bonaa KH, Ueland PM, Forde OH, Nordrehaug JE (1995) Serum total homocysteine and coronary heart disease. Int J Epidemiol 24(4):704–709

    Article  PubMed  CAS  Google Scholar 

  • Barbujani G, Nasidze IS, Whitehead GN (1994) Genetic diversity in the Caucasus. Hum Biol 66(4):639–668

    PubMed  CAS  Google Scholar 

  • Bauduer F, Lacombe D (2005) Factor V Leiden, prothrombin 20210A, methylenetetrahydrofolate reductase 677T and population genetics. Mol Genet Metab 86(1–2):91–99

    Article  PubMed  CAS  Google Scholar 

  • Bu R, Gutierrez MI, Al-Rasheed M, Belgaumi A, Bhatia K (2004) Variable drug metabolism genes in Arab population. Pharmacogenomics J 4(4):260–266

    Article  PubMed  CAS  Google Scholar 

  • Bulayeva KB (2006) Overview of genetic-epidemiological studies in ethnically and demographically diverse isolates of Dagestan, Northern Caucasus. Russia. Croat Med J 47(4):641–648

    Google Scholar 

  • Chou YC, Wu MH, Yu JC, Lee MS, Yang T, Shih HL, Wu TY, Sun CA (2006) Genetic polymorphisms of the methylenetetrahydrofolate reductase gene, plasma folate levels and breast cancer susceptibility: a case-control study in Taiwan. Carcinogenesis 27(11):2295–2300

    Article  PubMed  CAS  Google Scholar 

  • Dajani R, Fatahallah R, Dajani A, Al-Shboul M, Khader Y (2012) Prevalence of coagulation factor II G20210A and factor V G1691A Leiden polymorphisms in Chechans, a genetically isolated population in Jordan. Mol Biol Rep 39(9):9133–9138

    Article  PubMed  CAS  Google Scholar 

  • Dajani R, Arafat A, Hakooz N, Al-Abbadi Z, Yousef A, El Khateeb M, Quadan F (2013) Polymorphisms in factor II and factor V thrombophilia genes among Circassians in Jordan. J Thromb Thrombolysis 35(1):83–89

    Article  PubMed  CAS  Google Scholar 

  • de Bree A, Verschuren WM, Bjorke-Monsen AL, van der Put NM, Hell SG, Trijbels FJ, Blom HJ (2003) Effect of the methylenetetrahydrofolate reductase 677C→T mutation on the relations among folate intake and plasma folate and homocysteine concentrations in a general population sample. Am J Clin Nutr 77(3):687–693

    PubMed  Google Scholar 

  • den Heijer M, Koster T, Blom HJ, Bos GM, Briet E, Reitsma PH, Vandenbroucke JP, Rosendaal FR (1996) Hyperhomocysteinemia as a risk factor for deep-vein thrombosis. N Engl J Med 334(12):759–762

    Article  Google Scholar 

  • Dissanayake VH, Weerasekera LY, Gammulla CG, Jayasekara RW (2009) Prevalence of genetic thrombophilic polymorphisms in the Sri Lankan population: implications for association study design and clinical genetic testing services. Exp Mol Pathol 87(2):159–162

    Article  PubMed  CAS  Google Scholar 

  • Eid SS, Rihani G (2004) Prevalence of factor V Leiden, prothrombin G20210A, and MTHFR C677T mutations in 200 healthy Jordanians. Clin Lab Sci 17(4):200–202

    PubMed  Google Scholar 

  • Engbersen AM, Franken DG, Boers GH, Stevens EM, Trijbels FJ, Blom HJ (1995) Thermolabile 5,10-methylenetetrahydrofolate reductase as a cause of mild hyperhomocysteinemia. Am J Hum Genet 56(1):142–150

    PubMed  CAS  Google Scholar 

  • Falik-Zaccai TC, Haron Y, Eilat D, Harash B, Golinker E, Hussein O, Elsikovits R, Borochowitz Z, Linn S (2003) Coronary heart disease among Circassians in Israel is not associated with mutations in thrombophilia genes. Hum Biol 75(1):57–68

    Article  PubMed  Google Scholar 

  • Frosst P, Blom HJ, Milos R, Goyette P, Sheppard CA, Matthews RG, Boers GJ, den Heijer M, Kluitjmans LA, van den Heuvel LP (1995) A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 10(1):111–113

    Article  PubMed  CAS  Google Scholar 

  • Genest JJ Jr, McNamara JR, Salem DN, Wilson PW, Schaefer EJ, Malinow MR (1990) Plasma homocysteine levels in men with premature coronary artery disease. J Am Coll Cardiol 16(5):1114–1119

    Article  PubMed  Google Scholar 

  • Gueant-Rodriguez RM, Gueant JL, Debard R, Thirion S, Hong LX, Bronowicki JP, Namour F, Chabi NW, Sanni A, Anello G, Bosco P, Romano C, Amouzou E, Arrieta HR, Sanchez BE, Romano A, Herbeth B, Guilland JC, Mutchinick OM (2006) Prevalence of methylenetetrahydrofolate reductase 677T and 1298C alleles and folate status: a comparative study in Mexican, West African, and European populations. Am J Clin Nutr 83(3):701–707

    PubMed  CAS  Google Scholar 

  • Herrmann FH, Salazar-Sanchez L, Schuster G, Jimenez-Arce G, Grimm R, Gomez X, Chavez M, Wulff K, Schroder W (2004) Prevalence of eight molecular markers associated with thrombotic diseases in six Amerindian tribes and two African groups of Costa Rica. Am J Hum Biol 16(1):82–86

    Article  PubMed  Google Scholar 

  • Hessner MJ, Luhm RA, Pearson SL, Endean DJ, Friedman KD, Montgomery RR (1999) Prevalence of prothrombin G20210A, factor V G1691A (Leiden), and methylenetetrahydrofolate reductase (MTHFR) C677T in seven different populations determined by multiplex allele-specific PCR. Thromb Haemost 81(5):733–738

    PubMed  CAS  Google Scholar 

  • Hughes LB, Beasley TM, Patel H, Tiwari HK, Morgan SL, Baggott JE, Saag KG, McNicholl J, Moreland LW, Alarcon GS, Bridges SL Jr (2006) Racial or ethnic differences in allele frequencies of single-nucleotide polymorphisms in the methylenetetrahydrofolate reductase gene and their influence on response to methotrexate in rheumatoid arthritis. Ann Rheum Dis 65(9):1213–1218

    Article  PubMed  CAS  Google Scholar 

  • Kailani W (2002) Chechens in the Middle East: between original and host cultures. Caspian Studies Program event report. Harvard University, Cambridge

    Google Scholar 

  • Kang SS, Passen EL, Ruggie N, Wong PW, Sora H (1993) Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease. Circulation 88(4 Pt 1):1463–1469

    Article  PubMed  CAS  Google Scholar 

  • Kelemen LE, Anand SS, Hegele RA, Stampfer MJ, Rosner B, Willett WC, Montague PA, Lonn E, Vuksan V, Teo KK, Devannesen S, Yusuf S (2004) Associations of plasma homocysteine and the methylenetetrahydrofolate reductase C677T polymorphism with carotid intima media thickness among South Asian, Chinese and European Canadians. Atherosclerosis 176(2):361–370

    Article  PubMed  CAS  Google Scholar 

  • Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, den Heijer M, Trijbels FJ, Rozen R, Blom HJ (1996) Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 58(1):35–41

    PubMed  CAS  Google Scholar 

  • Lane DA, Mannucci PM, Bauer KA, Bertina RM, Bochkov NP, Boulyjenkov V, Chandy M, Dahlback B, Ginter EK, Miletich JP, Rosendaal FR, Seligsohn U (1996) Inherited thrombophilia, Part 1. Thromb Haemost 76(5):651–662

    PubMed  CAS  Google Scholar 

  • Nasidze I, Ling EY, Quinque D, Dupanloup I, Cordaux R, Rychkov S, Naumova O, Zhukova O, Sarraf-Zadengan N, Naderi GA, Asgary S, Sardas SM, Farhud DD, Sarkisian T, Asadov C, Kerimov A, Stoneking M (2004) Mitochondrial DNA and Y-chromosome variation in the Caucasus. Ann Hum Genet 68(3):205–221

    Article  PubMed  CAS  Google Scholar 

  • Ray JG (1998) Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med 158(19):2101–2106

    Article  PubMed  CAS  Google Scholar 

  • Robinson K, Mayer EL, Miller DP, Green R, van Lente F, Gupta A, Kottke-Marchane K, Savon SR, Selhub J, Nissen SE (1995) Hyperhomocysteinemia and low pyridoxal phosphate: common and independent reversible risk factors for coronary artery disease. Circulation 92(10):2825–2830

    Article  PubMed  CAS  Google Scholar 

  • van der Put NM, Steegers-Theunissen RP, Frosst P, Trijbels FJ, Eskes TK, van den Heuvel LP, Mariman EC, den Heyer M, Rozen R, Blom HJ (1995) Mutated methylenetetrahydrofolate reductase as a risk factor for spina bifida. Lancet 346(8982):1070–1071

    Article  PubMed  Google Scholar 

  • Van Guelpen B, Hultdin J, Johansson I, Hallmans G, Stenling R, Riboli E, Winkvist A, Palmqvist R (2006) Low folate levels may protect against colorectal cancer. Gut 55(10):1461–1466

    Article  PubMed  Google Scholar 

  • Verhoef P, Stampfer MJ, Buring JE, Gaziano JM, Allen RH, Stabler SP, Reynolds RD, Kok FJ, Hennekens CH, Willett WC (1996) Homocysteine metabolism and risk of myocardial infarction: relation with vitamins B6, B12, and folate. Am J Epidemiol 143(9):845–859

    Article  PubMed  CAS  Google Scholar 

  • Welch GN, Loscalzo J (1998) Homocysteine and atherothrombosis. N Engl J Med 338(15):1042–1050

    Article  PubMed  CAS  Google Scholar 

  • Whitehead AS, Gallagher P, Millis JL, Kirke PN, Burke H, Molloy AM, Weir DG, Shields DC, Scott JM (1995) A genetic defect in 5,10-methylenetetrahydrofolate reductase in neural tube defects. QJM 88(11):763–766

    PubMed  CAS  Google Scholar 

  • Wilcken B, Bamforth F, Li Z, Zhu H, Ritvanen A, Renlund M, Stoll C, Alembik Y, Dot B, Czeizel AE, Gelman-Kohan Z, Scarano G, Bianca S, Ettore G, Tenconi R, Bellato S, Scala I, Mutchinick OM, Lopez MA, de Walle H, Hofstra R, Joutchenko L, Kavteladze L, Bermejo E, Martinez-Frias ML, Gallagher M, Erickson JD, Vollset SE, Mastroiacovo P, Andria G, Botto LD (2003) Geographical and ethnic variation of the 677C→T allele of 5,10-methylenetetrahydrofolate reductase (MTHFR): findings from over 7000 newborns from 16 areas worldwide. J Med Genet 40(8):619–625

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study has been supported by the Hashemite University, Zarqa, Jordan. We would like to thank the Circassian and Chechen communities for their participation in this study. We would also like to thank the National Center for Diabetes, Genetics and Endocrinology, Amman, Jordan for allowing us to use their facilities.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rana Dajani.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Dajani, R., Fathallah, R., Arafat, A. et al. Prevalence of MTHFR C677T Single Nucleotide Polymorphism in Genetically Isolated Populations in Jordan. Biochem Genet 51, 780–788 (2013). https://doi.org/10.1007/s10528-013-9606-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-013-9606-9

Keywords

Navigation