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Evaluation of Human FcγRIIA (CD32) and FcγRIIIB (CD16) Polymorphisms in Caucasians and African-Americans Using Salivary DNA

机译:使用唾液DNA评估白种人和非裔美国人中人FcγRIIA(CD32)和FcγRIIIB(CD16)多态性

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Two classes of low-affinity receptors for the Fc region of immunoglobulin G (IgG) (FcγR) are constitutively expressed on resting human neutrophils. These receptors, termed FcγRIIa (CD32) and FcγRIIIb (CD16), display biallelic polymorphisms which have functional consequences with respect to binding and/or ingestion of targets opsonized by human IgG subclass antibodies. The H131-R131 polymorphism of CD32 influences binding of human IgG2 and, to a lesser extent, human IgG3 to neutrophils. The neutrophil antigen (NA1-NA2) polymorphism of CD16 influences the efficiency of phagocytosis of bacteria opsonized by human IgG1 and IgG3. These polymorphisms may influence host susceptibility to certain infectious and/or autoimmune diseases, prompting interest in the development of facile methods for determination of CD32 and CD16 genotype in various clinical settings. We previously reported that genomic DNA from saliva is a suitable alternative to DNA from blood in PCR-based analyses of CD32 and CD16 polymorphisms. In the present study, we utilized for the first time this salivary DNA-based methodology to define CD32 and CD16 genotypes in 271 Caucasian and 118 African-American subjects and to investigate possible linkage disequilibrium between certain CD32 and CD16 genotypes in these two ethnic groups. H131 and R131 gene frequencies were 0.45 and 0.55, respectively, among Caucasians and 0.59 among African-Americans. NA1 and NA2 gene frequencies were 0.38 and 0.62 among Caucasians and 0.39 and 0.61 among African-Americans. Since FcγRIIa and FcγRIIIb synergize in triggering neutrophils, we also assessed the frequency of different CD32 and CD16 genotype combinations in these two groups. In both groups, the R/R131-NA2/NA2 genotype combination was more common than the H/H131-NA1/NA1 combination (threefold for Caucasians versus sevenfold for African-Americans). Whether individuals with the combined R/R131-NA2/NA2 genotype are at greater risk for development of infectious and/or autoimmune diseases requires further investigation, which can be conveniently performed using DNA from saliva rather than blood.
机译:免疫球蛋白G(IgG)(FcγR)Fc区的两类低亲和力受体在静止的人嗜中性粒细胞上组成性表达。这些被称为FcγRIIa(CD32)和FcγRIIIb(CD16)的受体表现出双等位基因多态性,它们对人IgG亚类抗体调理的靶标的结合和/或摄取具有功能性后果。 CD32的H131-R131多态性影响人IgG2的结合,并在较小程度上影响人IgG3与嗜中性粒细胞的结合。 CD16的嗜中性粒细胞抗原(NA1-NA2)多态性影响被人IgG1和IgG3调理的细菌的吞噬效率。这些多态性可能会影响宿主对某些传染性和/或自身免疫性疾病的敏感性,从而引起人们对在各种临床环境中测定CD32和CD16基因型的简便方法的兴趣。我们先前曾报道,在基于PCR的CD32和CD16多态性分析中,唾液基因组DNA是血液DNA的合适替代物。在本研究中,我们首次利用这种基于唾液DNA的方法来定义271名白种人和118名非裔美国人受试者的CD32和CD16基因型,并研究这两个种族中某些CD32和CD16基因型之间可能存在的连锁不平衡。 H131和R131基因频率在白种人中分别为0.45和0.55,在非裔美国人中为0.59。白人的NA1和NA2基因频率分别为0.38和0.62,非裔美国人为0.39和0.61。由于FcγRIIa和FcγRIIIb在触发中性粒细胞中具有协同作用,因此我们还评估了这两组中不同CD32和CD16基因型组合的频率。在两组中,R / R131-NA2 / NA2基因型组合均比H / H131-NA1 / NA1组合更为普遍(高加索人为三倍,非裔美国人为七倍)。具有合并的R / R131-NA2 / NA2基因型的个体是否更有发展感染性和/或自身免疫性疾病的风险,需要进一步研究,可以使用唾液中的DNA而不是血液来方便地进行研究。

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