Interethnic diversity of the CD209 (rs4804803) gene promoter polymorphism in African but not American sickle cell disease

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.

Keywords: Africa; African Americans; CD209; Caucasians; Co-morbidities; Diversity; Interethnic; Populations; Sickle cell disease.

Figure 1. Genotypic distribution of CD209 gene promoter polymorphism (SNP-336 A/G; rs4804803) in Caucasian, African American and African healthy controls.

Amplified PCR products were digested with MscI restriction endonuclease (Fisher Scientific, Waltham, Massachusetts, USA), and expressed on a 2% ethidium bromide-stained agarose gel. Homozygote wild type variant (snp-336A) showed no digestion (150 bp); homozygote mutant variant (snp-336G) produced two bands (131 and 19 bp) on digestion (lower band size not shown). Marker: 100 bp ladder, where the 500 bp band stains most intensely (New England Biolabs, Ipswich, Massachusetts, USA). Black bars: Africans; blue bars: African Americans; red bars: Caucasians.

Figure 2. Genotypic frequency of CD209 gene promoter polymorphism (SNP-336 A/G; rs4804803) among African sickle cell disease and control groups.

Amplified PCR products were digested with MscI restriction endonuclease (Fisher Scientific, Waltham, Massachusetts, USA), and expressed on a 2% ethidium bromide-stained agarose gel. Homozygote wild type variant (snp-336A) showed no digestion (150 bp); homozygote mutant variant (snp-336G) produced two bands (131 and 19 bp) on digestion (lower band size not shown). Marker: 100 bp ladder, where the 500 bp band stains most intensely (New England Biolabs). Blue bars-sickle cell disease; red bars-control groups.

Figure 3. Genotypic frequency of CD209 gene promoter polymorphisms (SNP-336 A/G; rs4804803) among African American sickle cell disease and control groups.