Lucas Sandri Thaisa, Adukpo Selorme, Giang Dao Phuong, Nguetse Christian N, Antunes Andrade Fabiana, Tong Hoang van, Toan Nguyen Linh, Song Le Huu, Elumalai Preetham, Thangaraj Kumarasamy, Valluri Vijaya Lakshmi, Ntoumi Francine, Meyer Christian G, Jose de Messias Reason Iara, Kremsner Peter G, Velavan Thirumalaisamy P
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
Laboratory of Molecular Immunopathology, Federal University of Paraná, Curitiba, Brazil.
PLoS One. 2017 May 17;12(5):e0175973. doi: 10.1371/journal.pone.0175973. eCollection 2017.
Pathogens exert selective pressure which may lead to substantial changes in host immune responses. The human complement receptor type 1 (CR1) is an innate immune recognition glycoprotein that regulates the activation of the complement pathway and removes opsonized immune complexes. CR1 genetic variants in exon 29 have been associated with expression levels, C1q or C3b binding and increased susceptibility to several infectious diseases. Five distinct CR1 nucleotide substitutions determine the Knops blood group phenotypes, namely Kna/b, McCa/b, Sl1/Sl2, Sl4/Sl5 and KCAM+/-.
CR1 variants were genotyped by direct sequencing in a cohort of 441 healthy individuals from Brazil, Vietnam, India, Republic of Congo and Ghana.
The distribution of the CR1 alleles, genotypes and haplotypes differed significantly among geographical settings (p≤0.001). CR1 variants rs17047660A/G (McCa/b) and rs17047661A/G (Sl1/Sl2) were exclusively observed to be polymorphic in African populations compared to the groups from Asia and South-America, strongly suggesting that these two SNPs may be subjected to selection. This is further substantiated by a high linkage disequilibrium between the two variants in the Congolese and Ghanaian populations. A total of nine CR1 haplotypes were observed. The CR1AGAATA haplotype was found more frequently among the Brazilian and Vietnamese study groups; the CR1AGAATG haplotype was frequent in the Indian and Vietnamese populations, while the CR1*AGAGTG haplotype was frequent among Congolese and Ghanaian individuals.
The African populations included in this study might have a selective advantage conferred to immune genes involved in pathogen recognition and signaling, possibly contributing to disease susceptibility or resistance.
病原体施加选择性压力，这可能导致宿主免疫反应发生重大变化。人类1型补体受体（CR1）是一种先天性免疫识别糖蛋白，可调节补体途径的激活并清除调理素化的免疫复合物。外显子29中的CR1基因变异与表达水平、C1q或C3b结合以及对几种传染病易感性增加有关。五个不同的CR1核苷酸替换决定了诺普斯血型表型，即Kna/b、McCa/b、Sl1/Sl2、Sl4/Sl5和KCAM+/-。
通过直接测序对来自巴西、越南、印度、刚果共和国和加纳的441名健康个体组成的队列中的CR1变异进行基因分型。
CR1等位基因、基因型和单倍型的分布在不同地理区域之间存在显著差异（p≤0.001）。与亚洲和南美群体相比，CR1变异rs17047660A/G（McCa/b）和rs17047661A/G（Sl1/Sl2）仅在非洲人群中观察到多态性，强烈表明这两个单核苷酸多态性可能受到选择。刚果和加纳人群中这两个变异之间的高连锁不平衡进一步证实了这一点。总共观察到9种CR1单倍型。CR1AGAATA单倍型在巴西和越南研究组中更常见；CR1AGAATG单倍型在印度和越南人群中常见，而CR1*AGAGTG单倍型在刚果和加纳个体中常见。
本研究中纳入的非洲人群可能对参与病原体识别和信号传导的免疫基因具有选择性优势，这可能导致疾病易感性或抵抗力的差异。
