Department of Biomedical Sciences, College of Health Sciences and Technology, Rochester Institute of Technology , Rochester, NY , USA.
Centre de Recherche et de Lutte contre la Drepanocytose , Bamako , Mali.
PeerJ. 2015 Feb 24;3:e799. doi: 10.7717/peerj.799. eCollection 2015.
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.
阐明 CD209 基因启动子多态性的基因组多样性有助于阐明疾病的病理生理学机制以及对合并症的贡献。CD209 基因启动子多态性与感染易感性有关。我们假设 CD209 突变变体在非洲人和镰状细胞病患者中更为常见。我们分析了来自马里的 145 名镰状细胞病患者和 231 名健康对照者、331 名镰状细胞病患者和 379 名非裔美国人健康对照者以及 159 名白种人健康对照者的 CD209 基因（rs4804803）的频率，并确定了与疾病的相关性。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对组内和组间进行比较分析。根据种族多样化，我们发现 CD209（snp309A/G）基因启动子的纯合突变变体的基因型（23.4%对 16.9%对 3.2%）和等位基因频率（48.7%对 42.1%对 19.8%）在非洲人、非裔美国人和白种人之间存在显著差异。疾病组与对照组的比较评估显示，在非洲镰状细胞病患者和健康对照组中，纯合突变变体的基因型（10.4%对 23.4%；p=0.002）和等位基因频率（39.7%对 48.7%；p=0.02）存在显著差异，而这一观察结果在美国人群中完全不存在。比较疾病组时，我们发现非洲人和非裔美国人镰状细胞病患者之间的 CD209 纯合突变变体的基因型（p=0.19）或等位基因（p=0.72）频率没有差异。非洲对照组中 CD209 纯合突变变体的更高频率揭示了对感染性疾病产生免疫反应的能力可能受损，并且可能在组内和组间划定了对感染性合并症的易感性或严重程度。
