Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients
Disparate distribution of 16 candidate single nucleotide polymorphisms among racial and ethnic groups of pediatric heart transplant patients
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DOI：
10.1097/01.tp.0000250656.33731.08
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发表时间：
2006-12-27
期刊：
影响因子：
6.2
通讯作者：
Zeevi, Adriana
中科院分区：
文献类型：
--
作者：
Girnita, Diana M.;Webber, Steven A.;Zeevi, Adriana
背景资料。非洲裔美国人的同种异体移植失败率仍然高于高加索人。单核苷酸多态(SNPs)与同种异体移植结果的改变有关。在这项多中心研究中，我们比较了来自三个民族/种族的364名儿童心脏移植受者的SNP频率：高加索人(n=243)、非裔美国人(n=39)和西班牙裔人(n=82)。靶基因分别为：肿瘤坏死因子-α、白介素10、白介素6、干扰素-γ、血管内皮生长因子、转化生长因子-β1、Fas、FasL、颗粒酶B、ABCBI、细胞色素P3A5。与高加索人相比，非裔美国人表现出与低表达干扰素-γ(24%比45.7%，P<；0.001)和IL-10(33%比57.1%，P=0.052)相关的更高的基因频率。非洲裔美国人也表现出高IL-6的患病率增加(82.9%vs.38.1%；P<；0.001)。血管内皮生长因子-2578C/C和-460C/C基因型在非裔美国人和拉美裔美国人中的频率高于高加索人(P<；0.001)。Fas的G/G型和FasL的T/T型在非裔美国人的受者中表达更多。颗粒酶B(-295A/G)基因在三组中的分布差异有统计学意义。与高加索人相比，非裔美国人携带ABCBI2677G/G基因的可能性是高加索人的两倍(78.6%比33.7%，P<；0.0025)，而且他们是更常见的CYP3A5*1/*1基因携带者(35.7%对0.6%在高加索人，7.2%在西班牙裔；P<；0.001)。非裔美国人的遗传背景可能倾向于促炎/较低的调节环境，减少药物暴露和免疫抑制效果。在这项正在进行的多中心研究中，这些基因多态在种族/种族群体之间的差异正在被记录下来，以便设计治疗策略来优化儿科移植接受者的结果。
Background. Allograft failure in African-Americans remains higher than in Caucasians. Single nucleotide polymorphisms (SNPs) have been associated with altered allograft outcomes.Methods. In this multi-center study we compared SNP frequencies in 364 pediatric heart recipients from three ethnic/racial groups: Caucasian (n = 243), African-American (n = 39), and Hispanic (n = 82). The target genes were: tumor necrosis factor-alpha, interleukin (IL)-10, IL-6, interferon (IFN)-gamma, vascular endothelial growth factor (VEGF), transforming growth factor-P I, Fas, FasL, granzyme B, ABCBI, CYP3A5.Results. Compared to Caucasians, African-Americans exhibited a higher prevalence of genotypes associated with low expression of IFN-gamma (24% vs. 45.7%, P < 0.001) and IL-10 (33% vs. 57.1%, P=0.052). African-Americans also exhibited an increased prevalence of high IL-6 (82.9%vs. 38.1%;P < 0.001). VEGF -2578 C/C and -460 C/C genotypes were found more frequently in African-Americans and Hispanics as compared to Caucasians (P < 0.001). G/G genotype of Fas and T/T genotype of FasL, were expressed more often by African-American recipients. The prevalence of Granzyme B (-295A/G) genotype was differentially distributed in the three groups. Compared with Caucasians, African-Americans were twice as likely to carry the ABCBI 2677 G/G genotype (78.6% vs. 33.7%, P < 0.0025), and they were more frequent carriers of the CYP3A5 *1/*1 genotype (35.7% vs. 0.6% in Caucasians and 7.2% in Hispanics; P < 0.001).Conclusion. African-Americans have a genetic background that may predispose to proinflammatory/lower regulatory environment, reduced drug exposure and immunosuppressive efficacy. In this ongoing multicenter study, these gene polymorphisms differences among ethnic/racial groups are being documented so that therapeutic strategies can be devised to optimize outcomes for pediatric transplant recipients.