Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.

Hemoglobinopathies, merozoite surface protein-2 gene polymorphisms, and acquisition of Epstein Barr virus among infants in Western Kenya.
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DOI:
10.1186/s12885-023-11063-2
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发表时间:
2023-06-20
期刊:
影响因子:
3.8
通讯作者:
Ouma, Collins
Ouma, Collins
中科院分区:
医学2区
文献类型:
--
作者:
Olewe, Perez K.;Awandu, Shehu Shagari;Munde, Elly O.;Anyona, Samuel B.;Raballah, Evans;Amolo, Asito S.;Ogola, Sidney;Ndenga, Erick;Onyango, Clinton O.;Rochford, Rosemary;Perkins, Douglas J.;Ouma, Collins

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爱泼斯坦-巴尔病毒(EBV)相关的地方性Burkitt淋巴瘤儿童癌症与居住在肯尼亚西部恶性疟原虫全流行地区的儿童的发病率和死亡率有关。恶性疟原虫对镰状细胞性状(SCT)、α地中海贫血(-α3.7/αα)、葡萄糖-6-磷酸脱氢酶(G6PD)和裂殖子表面蛋白2(MSP-2)变异体(FC27、3D7)施加了很强的选择压力,从而降低了疟疾的严重程度。目前的研究验证了SCT、(-α3.7/αα)、G6PD突变和(MSP-2)变异(FC27、3D7)与早期EB病毒感染相关的假设。有关婴儿EB病毒感染状况的数据(6个月大的 和6-12个月大的≥ )是从先前的纵向研究中提取的。采用婴儿DNA存档(n = 81)和母亲DNA存档(n = 70)样本,对血红蛋白病和MSP-2进行基因分型。母亲DNA样本中MSP-2基因的存在被用来指示婴儿宫内疟疾的暴露。用TaqMan法或标准聚合酶链式反应检测基因变异。组间差异采用卡方检验或Fisher‘s分析。双变量回归模型被用来确定遗传变异体携带和EBV获得之间的关系。婴儿 < 6个月的EB病毒感染与-α3.7/αα(OR = 1.824,P = 0.354)、SCT(OR = 0.897,P = 0.881)或G6PD[Viangchan(871G &> A)/Chinese(1024C &> T)(OR = 2.614,P = 0.212)]和[Union(1360C &> T)/开平(1388G > A)(OR = 0.321,P = 0.295)]。宫内暴露于FC27(OR = 0.922,P = 0.914)或3D7(OR = 0.933,P = 0.921)与EB病毒感染无关。此外,婴儿 ≥ 6-12个月的EB病毒感染与-α3.7/αα(OR = 0.681,P = 0.442)、SCT(OR = 0.513,P = 0.305)、G6PD[(Viangchan(871G &> A)/Chinese(1024C &> T)(OR = 0.640,P = 0.677)]、[Mahidol(487G &> A)/Coimbra(592C &>T; T)(OR = 0.948,P = 0.940)],[(联合(1360C &>; T)/开平(1388G > A)(OR = 1.221,P = 0.768)]、非洲A(OR = 0.278,P = 0.257)],或宫内暴露于FC27(OR = 0.780,P = 0.662)或3D7(OR = 0.549,P = 0.241)。虽然血红蛋白疾病(-α3.7/αα、SCT和G6PD突变)和宫内暴露于MSP-2与0-12个月婴儿感染EB病毒无关,但在肯尼亚西部的人群中发现了新的G6PD变异。为了确定已知的和新的血红蛋白疾病以及宫内暴露的MSP-2不会增加对EBV的易感性,未来需要从多个地点进行更大样本量的研究,采用全基因组分析。网上版载有补充材料,可在10.1186/s12885-023-11063-2查阅。
Epstein Barr virus (EBV)-associated endemic Burkitt’s Lymphoma pediatric cancer is associated with morbidity and mortality among children resident in holoendemic Plasmodium falciparum regions in western Kenya. P. falciparum exerts strong selection pressure on sickle cell trait (SCT), alpha thalassemia (-α3.7/αα), glucose-6-phosphate dehydrogenase (G6PD), and merozoite surface protein 2 (MSP-2) variants (FC27, 3D7) that confer reduced malarial disease severity. The current study tested the hypothesis that SCT, (-α3.7/αα), G6PD mutation and (MSP-2) variants (FC27, 3D7) are associated with an early age of EBV acquisition. Data on infant EBV infection status (< 6 and ≥ 6–12 months of age) was abstracted from a previous longitudinal study. Archived infant DNA (n = 81) and mothers DNA (n = 70) samples were used for genotyping hemoglobinopathies and MSP-2. The presence of MSP-2 genotypes in maternal DNA samples was used to indicate infant in-utero malarial exposure. Genetic variants were determined by TaqMan assays or standard PCR. Group differences were determined by Chi-square or Fisher’s analysis. Bivariate regression modeling was used to determine the relationship between the carriage of genetic variants and EBV acquisition. EBV acquisition for infants < 6 months was not associated with -α3.7/αα (OR = 1.824, P = 0.354), SCT (OR = 0.897, P = 0.881), or G6PD [Viangchan (871G > A)/Chinese (1024 C > T) (OR = 2.614, P = 0.212)] and [Union (1360 C > T)/Kaiping (1388G > A) (OR = 0.321, P = 0.295)]. There was no relationship between EBV acquisition and in-utero exposure to either FC27 (OR = 0.922, P = 0.914) or 3D7 (OR = 0.933, P = 0.921). In addition, EBV acquisition in infants ≥ 6–12 months also showed no association with -α3.7/αα (OR = 0.681, P = 0.442), SCT (OR = 0.513, P = 0.305), G6PD [(Viangchan (871G > A)/Chinese (1024 C > T) (OR = 0.640, P = 0.677)], [Mahidol (487G > A)/Coimbra (592 C > T) (OR = 0.948, P = 0.940)], [(Union (1360 C > T)/Kaiping (1388G > A) (OR = 1.221, P = 0.768)], African A (OR = 0.278, P = 0.257)], or in utero exposure to either FC27 (OR = 0.780, P = 0.662) or 3D7 (OR = 0.549, P = 0.241). Although hemoglobinopathies (-α3.7/αα, SCT, and G6PD mutations) and in-utero exposure to MSP-2 were not associated with EBV acquisition in infants 0–12 months, novel G6PD variants were discovered in the population from western Kenya. To establish that the known and novel hemoglobinopathies, and in utero MSP-2 exposure do not confer susceptibility to EBV, future studies with larger sample sizes from multiple sites adopting genome-wide analysis are required. The online version contains supplementary material available at 10.1186/s12885-023-11063-2.
DOI: 10.1038/ejhg.2009.8
发表时间: 2009-08
期刊: European journal of human genetics : EJHG
影响因子: --
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