Background The interaction between antibodies and Fc gamma receptors (FcγRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcγRs influence the host's capacity to control parasite infection. This study investigates whether non-coding variants influencing FcγR expression are associated with anti-malarial immunization and infection traits. Methods We utilized eQTL databases and functional annotations to identify non-coding variants, specifically rs1771575, rs2099684, and rs6700241, within the FCGR gene cluster. In addition, we examined the coding variants rs1801274 (p.His167Arg) and rs1050501 (p.Ile231Thr), which affect the affinity of FcγRIIa and FcγRIIb for IgG. These variants were genotyped in 163 individuals from Burkinabe families. Family-based linear mixed regression and Quantitative Transmission Disequilibrium Tests (QTDT) analyses were performed to assess associations with IgG levels and malaria infection, accounting for relevant covariates. Results Linear mixed models identified rs1771575 as associated with total IgG levels, while both rs1771575 and rs1801274 were linked to IgG2, and rs1050501 to IgG1 levels. A haplotype combining rs2099684 and rs6700241 was positively associated with IgG1. The rs1771575-CC and rs1050501-TT genotypes correlated with higher infection levels in children. QTDT models confirmed the association of rs1771575 with IgG2 and infection in children. Conclusions Our findings suggest that the intergenic variant rs1771575 serves as an independent marker for IgG levels and blood infection in children. This highlights the interplay between regulatory variants and coding mutations in FCGR, which may influence immune function and antibody production. These results underscore the potential for personalized strategies to monitor humoral responses in malaria-endemic regions.

中文翻译：

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Fc γ 受体基因的表达数量性状位点与布基纳法索家族的抗疟疾 IgG 反应和感染水平相关


背景抗体与 Fc γ 受体 （FcγRs） 之间的相互作用在调节对恶性疟原虫的免疫反应中起关键作用。编码 FcγRs 的基因多态性会影响宿主控制寄生虫感染的能力。本研究调查了影响 FcγR 表达的非编码变异是否与抗疟疾免疫和感染性状有关。方法 我们利用 eQTL 数据库和功能注释来识别 FCGR 基因簇中的非编码变异，特别是 rs1771575 、 rs2099684 和 rs6700241。此外，我们检查了编码变体 rs1801274 （p.His167Arg） 和 rs1050501 （p.Ile231Thr），它们影响 FcγRIIa 和 FcγRIIb 对 IgG 的亲和力。这些变异在来自布基纳法索家庭的 163 个个体中进行了基因分型。进行基于家庭的线性混合回归和定量传递不平衡测试 （QTDT） 分析，以评估与 IgG 水平和疟疾感染的关联，并考虑相关协变量。结果 线性混合模型确定 rs1771575 与总 IgG 水平相关，而 rs1771575 和 rs1801274 均与 IgG2 相关，rs1050501 与 IgG1 水平相关。结合 rs2099684 和 rs6700241 的单倍型与 IgG1 呈正相关。rs1771575-CC 和 rs1050501-TT 基因型与儿童较高的感染水平相关。QTDT 模型证实了 rs1771575 与儿童 IgG2 和感染的相关性。结论 我们的研究结果表明，基因间变异 rs1771575 是儿童 IgG 水平和血液感染的独立标志物。这突出了 FCGR 中调节变异和编码突变之间的相互作用，这可能会影响免疫功能和抗体产生。 这些结果强调了个性化策略在疟疾流行地区监测体液反应的潜力。