Reliable and rapid characterization of functional FCN2 gene variants reveals diverse geographical patterns

BMC Medical Genetics

Thirumalaisamy P Velavan²  Peter G Kremsner²  Jürgen FJ Kun²  Philipp Zanger²  Dennis Nurjadi²  Iara JT Messias-Reason⁵  Paola R Luz⁵  Le H Song³  Nguyen L Toan¹  Hoang Van Tong²  Eman Abou Ouf²  Olusola Ojurongbe⁴ 

[1]Department of Pathophysiology, Vietnam Military Medical University, Hanoi, Vietnam

[2]Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany

[3]Tran Hung Dao Hospital, Hanoi, Vietnam

[4]Ladoke Akintola University of Technology, Ogbomoso, Nigeria

[5]Laboratório de Imunopatologia Molecular-Hospital de Clínicas, Federal University of Paraná, Curitiba, Brazil

关键词: Distribution;    Haplotypes;    Genotypes;    Ficolin-2;    FRET;   

Others  :  1177858
DOI  :  10.1186/1471-2350-13-37

 received in 2012-01-25, accepted in 2012-04-23,  发布年份 2012

【 摘 要 】

Background

Ficolin-2 coded by FCN2 gene is a soluble serum protein and an innate immune recognition element of the complement system. FCN2 gene polymorphisms reveal distinct geographical patterns and are documented to alter serum ficolin levels and modulate disease susceptibility.

Methods

We employed a real-time PCR based on Fluorescence Resonance Energy Transfer (FRET) method to genotype four functional SNPs including -986 G > A (#rs3124952), -602 G > A (#rs3124953), -4A > G (#rs17514136) and +6424 G > T (#rs7851696) in the ficolin-2 (FCN2) gene. We characterized the FCN2 variants in individuals representing Brazilian (n = 176), Nigerian (n = 180), Vietnamese (n = 172) and European Caucasian ethnicity (n = 165).

Results

We observed that the genotype distribution of three functional SNP variants (−986 G > A, -602 G > A and -4A > G) differ significantly between the populations investigated (p < 0.0001). The SNP variants were highly linked to each other and revealed significant population patterns. Also the distribution of haplotypes revealed distinct geographical patterns (p < 0.0001).

Conclusions

The observed distribution of the FCN2 functional SNP variants may likely contribute to altered serum ficolin levels and this may depend on the different disease settings in world populations. To conclude, the use of FRET based real-time PCR especially for FCN2 gene will benefit a larger scientific community who extensively depend on rapid, reliable method for FCN2 genotyping.

【 授权许可】

   
2012 Ojurongbe et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Medzhitov R: Recognition of microorganisms and activation of the immune response. Nature 2007, 449:819-826.
• [2]Runza VL, Schwaeble W, Mannel DN: Ficolins: novel pattern recognition molecules of the innate immune response. Immunobiology 2008, 213:297-306.
• [3]Endo Y, Matsushita M, Fujita T: The role of ficolins in the lectin pathway of innate immunity. Int J Biochem Cell Biol 2011, 43:705-712.
• [4]Garred P, Honore C, Ma YJ, Rorvig S, Cowland J, Borregaard N, et al.: The genetics of ficolins. J Innate Immun 2009, 2:3-16.
• [5]Garlatti V, Belloy N, Martin L, Lacroix M, Matsushita M, Endo Y, et al.: Structural insights into the innate immune recognition specificities of L- and H-ficolins. EMBO J 2007, 26:623-633.
• [6]Ma YG, Cho MY, Zhao M, Park JW, Matsushita M, Fujita T, et al.: Human mannose-binding lectin and L-ficolin function as specific pattern recognition proteins in the lectin activation pathway of complement. J Biol Chem 2004, 279:25307-25312.
• [7]Krarup A, Thiel S, Hansen A, Fujita T, Jensenius JC: L-ficolin is a pattern recognition molecule specific for acetyl groups. J Biol Chem 2004, 279:47513-47519.
• [8]Munthe-Fog L, Hummelshoj T, Hansen BE, Koch C, Madsen HO, Skjodt K, et al.: The impact of FCN2 polymorphisms and haplotypes on the Ficolin-2 serum levels. Scand J Immunol 2007, 65:383-392.
• [9]Hummelshoj T, Munthe-Fog L, Madsen HO, Fujita T, Matsushita M, Garred P: Polymorphisms in the FCN2 gene determine serum variation and function of Ficolin-2. Hum Mol Genet 2005, 14:1651-1658.
• [10]Hummelshoj T, Munthe-Fog L, Madsen HO, Garred P: Functional SNPs in the human ficolin (FCN) genes reveal distinct geographical patterns. Mol Immunol 2008, 45:2508-2520.
• [11]Chen X, Katoh Y, Nakamura K, Oyama N, Kaneko F, Endo Y, et al.: Single nucleotide polymorphisms of Ficolin 2 gene in Behcet’s disease. J Dermatol Sci 2006, 43:201-205.
• [12]de Messias-Reason I, Kremsner PG, Kun JF: Functional haplotypes that produce normal ficolin-2 levels protect against clinical leprosy. J Infect Dis 2009, 199:801-804.
• [13]Faik I, Oyedeji SI, Idris Z, de Messias-Reason IJ, Lell B, Kremsner PG, et al.: Ficolin-2 levels and genetic polymorphisms of FCN2 in malaria. Hum Immunol 2011, 72:74-79.
• [14]Messias-Reason IJ, Schafranski MD, Kremsner PG, Kun JF: Ficolin 2 (FCN2) functional polymorphisms and the risk of rheumatic fever and rheumatic heart disease. Clin Exp Immunol 2009, 157:395-399.
• [15]Ruskamp JM, Hoekstra MO, Postma DS, Kerkhof M, Bottema RW, Koppelman GH, et al.: Exploring the role of polymorphisms in ficolin genes in respiratory tract infections in children. Clin Exp Immunol 2009, 155:433-440.
• [16]Hoang TV, Toan NL, Song LH, Ouf EA, Bock CT, Kremsner PG, et al.: Ficolin-2 levels and FCN2 haplotypes influence hepatitis B infection outcome in Vietnamese patients. PLoS One 2011, 6:e28113.
• [17]Assaf A, Hoang TV, Faik I, Aebischer T, Kremsner PG, Kun JF, et al.: Genetic evidence of functional ficolin-2 haplotype as susceptibility factor in cutaneous leishmaniasis. PLoS One 2012, 7:e34113.
• [18]Kwok PY: Methods for genotyping single nucleotide polymorphisms. Annu Rev Genomics Hum Genet 2001, 2:235-258.
• [19]Tsuchihashi Z, Dracopoli NC: Progress in high throughput SNP genotyping methods. Pharmacogenomics J 2002, 2:103-110.