Abstract
Elucidating the genomic diversity of CD209 gene promoter polymorphism could assist in clarifying disease pathophysiology as well as contribution to co-morbidities. CD209 gene promoter polymorphism has been shown to be associated with susceptibility to infection. We hypothesize that CD209 mutant variants occur at a higher frequency among Africans and in sickle cell disease. We analyzed the frequency of the CD209 gene (rs4804803) in healthy control and sickle cell disease (SCD) populations and determined association with disease. Genomic DNA was extracted from blood samples collected from 145 SCD and 231 control Africans (from Mali), 331 SCD and 379 control African Americans and 159 Caucasians. Comparative analysis among and between groups was carried out by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Per ethnic diversification, we found significant disparity in genotypic (23.4% versus 16.9% versus 3.2%) and allelic frequencies (48.7% versus 42.1% versus 19.8%) of the homozygote mutant variant of the CD209 (snp 309A/G) gene promoter between Africans, African Americans and Caucasians respectively. Comparative evaluation between disease and control groups reveal a significant difference in genotypic (10.4% versus 23.4%; p = 0.002) and allelic frequencies (39.7% versus 48.7%; p = 0.02) of the homozygote mutant variant in African SCD and healthy controls respectively, an observation that is completely absent among Americans. Comparing disease groups, we found no difference in the genotypic (p = 0.19) or allelic (p = 0.72) frequencies of CD209 homozygote mutant variant between Africans and Americans with sickle cell disease. The higher frequency of CD209 homozygote mutant variants in the African control group reveals a potential impairment of the capacity to mount an immune response to infectious diseases, and possibly delineate susceptibility to or severity of infectious co-morbidities within and between groups.
Highlights
Sickle cell disease (SCD) is an inherited multisystem disorder, characterized by chronic hemolytic anemia, vaso-occlusive crises and several other disease outcomes such as acute chest syndrome, bacteremia, leg ulcers and priapism (Bunn, 1997; Benkerrou et al, 2002)
We found a significant difference in the genetic diversity of the promoter variant of CD209 (DC-SIGN1-336A/G; rs4804803) gene polymorphism in different populations
Since clinical manifestation of sickle cell disease varies greatly within an individual, across individuals of the same population and those of different populations, we evaluated the diversity of CD209 gene promoter polymorphisms between sickle cell groups recruited from Africa and United States
Summary
Sickle cell disease (SCD) is an inherited multisystem disorder, characterized by chronic hemolytic anemia, vaso-occlusive crises and several other disease outcomes such as acute chest syndrome, bacteremia, leg ulcers and priapism (Bunn, 1997; Benkerrou et al, 2002). Other reports have shown that there is an over-stimulation of pro-inflammatory cytokines in sickle cell disease patients, which might be be related to vaso-occlusion (Makis, Hatzimichael & Bourantas, 2000; Pathare et al, 2004; Steinberg, 2006; Conran, Franco-Penteado & Costa, 2009; Qari, Dier & Mousa, 2012; Bandeira et al, 2014) This hyperstimulation has been associated with sickle cell haplotype in Brazil, and as such is the obvious consequence of worsening immune response to secondary infectious pathogens or co-morbidities of infection
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