The polymorphism rs2234767 (-1377 G>A) in the FAS gene may be associated with Plasmodium vivax infection in the Brazilian Amazon / O polimorfismo rs2234767 (-1377 G>A) no gene FAS pode estar associado à infecção por Plasmodium vivax na Amazônia brasileira

José Eduardo Gomes Arruda, Felipe Bonfim Freitas, Gustavo Capatti Cassiano, Ricardo Ishak, Ricardo Luiz Dantas Machado, Marinete Marins Póvoa, Antonio Carlos Rosário Vallinoto


The present study investigated the association between fatty acid synthase (FAS) and FAS ligand (FASL) gene polymorphisms in 128 and 99 individuals with and without Plasmodium vivax infection, respectively, in an endemic area of the Brazilian Amazon. Polymorphism genotyping was performed by real-time PCR (qPCR). Analysis of allele and genotype frequency distributions in the FAS-670 (A>G), FASL-844 (C>T) and FASL-124 (A>G) positions did not indicate statistically significant differences between the populations studied here. However, differences in the genotype frequencies of FAS-1377 G>A between the group of individuals infected with P. vivax and the control group were statistically significant (p = 0.007), suggesting an association between this polymorphism and susceptibility to infection.




Malaria, Plasmodium vivax, Polymorphism, Apoptosis.

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- Sivep. Malária. Sistema de Informação de Vigilância Epidemiológica [updated 2017 Jan 20]. Available from:

- Kern P, Dietrich M, Hemmer C, Wellinghausen N. Increased levels of soluble Fas ligand in serum in Plasmodium falciparum malaria. Infect. Immun. 2000; 68(5), 3061–63.

- Matsumoto J, Kawai S, Terao K, Kirinoki M, Yasutomi Y, Aikawa M, et al. Malaria infection induces rapid elevation of the soluble Fas ligand level in serum and subsequent T lymphocytopenia: possible factors responsible for the differences in susceptibility of two species of Macaca monkeys to Plasmodium coatneyi infection. Infect. Immun. 2000; 68(3), 1183-88.

- Riccio EKP, Júnior IN, Riccio LRP, das Graças Alecrim M, Corte-Real S, Morgado M, et al. Malaria associated apoptosis is not significantly correlated with either parasitemia or the number of previous malaria attacks. Parasitol. Res. 2003; 90(1), 9–18.

- Badley AD, Pilon AA, Landay A, Lynch, DH. Mechanisms of HIV-associated lymphocyte apoptosis. Blood. 2000; 96(9): 2951-64.

- Cossarizza A. Apoptosis and HIV infection: about molecules and genes. Curr. Pharm. Des. 2008; 14(3): 237-44.

- Zhang Z, Wang LE, Sturgis EM, El-Naggar AK, Hong WK, Amos CI, et al. Polymorphisms of FAS and FAS ligand genes involved in the death pathway and risk and progression of squamous cell carcinoma of the head and neck. Clin. Cancer Res. 2006; 12(18): 5596–602.

- Sibley K, Rollinson S, Allan JM, Smith AG, Law GR, Roddam PL, et al. Functional FAS promoter polymorphisms are associated with increased risk of acute myeloid leukemia. Cancer Res. 2003; 63(15); 4327-30.

- Wu J, Metz C, Xu X, Abe R, Gibson AW, Edberg JC, et al. A novel polymorphic CAAT/enhancerbinding protein beta element in the FasL gene promoter alters Fas ligand expression: a candidate background gene in African American systemic lupus erythematosus patients. J. Immunol. 2003; 170(1): 132-38.

- Pinti M, Troiano L, Nasi M, Moretti L, Monterastelli E, Mazzacani A, et al. Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: studies on centenarians. Cell. Death Differ. 2002; 9(4): 431–38.

- Cassiano GC, Santos EJ, Maia MH, Furini Ada C, Storti-Melo LM, Tomaz FM, et al. Impact of population admixture on the distribution of immune response co-stimulatory genes polymorphisms in a Brazilian population. Hum. Immunol. 2015; 76(11): 836-42.

- Wigginton JE, Cutler DJ, Abecasis GR. A note on exact tests of hardy-weinberg equilibrium. Am. J. Hum. Genet. 2005; 76(5): 887-93.

- Gonzalez JR, Armengol L, Sole X, Guino E, Mercader JM, Estivill X, et al. SNPassoc: an R package to perform whole genome association studies. Bioinformatics. 2007; 23(5): 644–45.

- Warnes G, Gorjanc F, Leisch M. Genetics: population genetics. [updated 2017 Jan 20] Available from:

- Sinnwell JP, Schaid DJ. Schaid, haplo.stats: Statistical analysis of haplotypes with traits and covariates when linkage phase is ambiguous. (accessed 20.01.17).

- Zhang X, Miao X, Sun T, Tan W, Qu S, Xiong P, et al. Functional polymorphisms in cell death pathway genes FAS and FASL contribute to risk of lung cancer. J. Med. Genet. 2005; 42(6), 479–84.

- Hashemi M, Fazaeli A, Ghavami S, Eskandari-Nasab E, Arbabi F, Mashhadi MA, et al. Functional polymorphisms of FAS and FASL gene and risk of breast cancer - pilot study of 134 cases. PLoS One. 2013; 8(1): e53075.

- Zhong-Xing Z, Yuan-Yuan M, Hai Zhen M, Jian-Gang Z, Li-Feng Z. FAS-1377 G/A (rs2234767) polymorphism and cancer susceptibility: a meta-analysis of 17,858 cases and 24,311 controls. PLoS One. 2013; 8(8): e73700.

- Yildir S, Sezgin M, Barlas IO, Turkoz G, Ankarali HC, Sahin G, et al. Relation of the Fas and FasL gene polymorphisms with susceptibility to and severity of rheumatoid arthritis. Rheumatol. Int. 2013; 33(10): 2637–45.

- Santana BB, Viegas ML, Conde SR, Ishak MO, Ishak R, Vallinoto AC. FAS and FASL gene polymorphisms are not associated with hepatitis B virus infection based on a case-control study in a Brazilian population. Dis. Markers. 2013; 35(6): 741-46.



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