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中缅边境疟疾高发与CR1、IL-1A、IL-4R、IL-4、NOS和TNF的多态性相关,但与葡萄糖-6-磷酸脱氢酶(G6PD)缺乏无关。

High Incidence of Malaria Along the Sino-Burmese Border Is Associated With Polymorphisms of CR1, IL-1A, IL-4R, IL-4, NOS, and TNF, But Not With G6PD Deficiency.

作者信息

Ren Na, Kuang Ying-Min, Tang Qiong-Lin, Cheng Long, Zhang Chun-Hua, Yang Zao-Qing, He Yong-Shu, Zhu Yue-Chun

机构信息

From the Department of Biochemistry and Molecular Biology (NR, LC, C-HZ, Q-LT, Z-QY, Y-SH, Y-CZ); and First Affiliated Hospital, Kunming Medical University, Kunming, Yunnan, PR China (Y-MK).

出版信息

Medicine (Baltimore). 2015 Oct;94(40):e1681. doi: 10.1097/MD.0000000000001681.

Abstract

Malaria is highly endemic in Yunnan Province, China, with the incidence of malaria being highest along the Sino-Burmese border. The aim of our study was to determine whether genetic polymorphisms are associated with the prevalence of malaria among Chinese residents of the Sino-Burmese border region. Fourteen otherwise healthy people with glucose-6-phosphate dehydrogenase (G6PD) deficiency, 50 malaria patients, and 67 healthy control subjects were included in our cross-sectional study. We analyzed the frequency of the G3093T and T520C single-nucleotide polymorphisms (SNPs) of CR1. Logistic regression was used to calculate the prevalence odds ratio (POR) and 95% confidence interval (CI) of malaria for the T520C SNP of CR1 and SNPs of G6PD, IL-4, IL-4R, IL-1A, NOS, CD40LG, TNF, and LUC7L. The frequency of the 3093T/3093T genotype of CR1 in the malaria group (0.16) was significantly higher than that in the control group (0.045, P < 0.05), and significantly lower than that in the G6PD deficiency group (0.43, P < 0.01). The frequency of the 520T/520T genotype of CR1 was significantly higher in the malaria patients (0.78) than that in the control group (0.67, P < 0.05) and G6PD-deficiency group (0.36, P < 0.05). The T allele of the T520C variant of CR1 was significantly associated with the prevalence of malaria (POR: 1.460; 95% CI: 0.703-3.034). Polymorphisms of G6PD did not significantly influence the prevalence malaria (P > 0.05). A GTGTGTC haplotype consisting of IL-1A (rs17561), IL-4 (rs2243250), TNF (rs1800750), IL-4R (rs1805015), NOS (rs8078340), CD40LG (rs1126535), and LUC7L (rs1211375) was significantly associated with the prevalence of malaria (POR: 1.822, 95% CI: 0.998-3.324). The 3093G/3093G and 520T/520T genotypes are the predominant genetic variants of CR1 among Chinese residents near the Sino-Burmese border, and the T allele of T520C is associated with the prevalence of malaria in this region. Although G6PD deficiency does not protect against malaria, it may diminish the association between malaria and the CR1 polymorphisms in this population. The GTGTGTC haplotype is also associated with the prevalence of malaria in this region.

摘要

疟疾在中国云南省高度流行,其中疟疾发病率最高的地区位于中缅边境。我们研究的目的是确定基因多态性是否与中缅边境地区中国居民的疟疾流行率相关。我们的横断面研究纳入了14名葡萄糖-6-磷酸脱氢酶(G6PD)缺乏的健康人、50名疟疾患者和67名健康对照者。我们分析了补体受体1(CR1)的G3093T和T520C单核苷酸多态性(SNP)的频率。采用逻辑回归计算CR1的T520C SNP以及G6PD、白细胞介素-4(IL-4)、IL-4受体(IL-4R)、白细胞介素-1α(IL-1A)、一氧化氮合酶(NOS)、CD40配体(CD40LG)、肿瘤坏死因子(TNF)和LUC7L的SNP的疟疾患病优势比(POR)和95%置信区间(CI)。疟疾组中CR1的3093T/3093T基因型频率(0.16)显著高于对照组(0.045,P<0.05),且显著低于G6PD缺乏组(0.43,P<0.01)。CR1的520T/520T基因型频率在疟疾患者中(0.78)显著高于对照组(0.67,P<0.05)和G6PD缺乏组(0.36,P<0.05)。CR1的T520C变异的T等位基因与疟疾流行率显著相关(POR:1.460;95%CI:0.703 - 3.034)。G6PD的多态性对疟疾流行率没有显著影响(P>0.05)。由IL-1A(rs17561)、IL-4(rs2243250)、TNF(rs1800750)、IL-4R(rs1805015)、NOS(rs8078340)、CD40LG(rs1126535)和LUC7L(rs1211375)组成的GTGTGTC单倍型与疟疾流行率显著相关(POR:1.822,95%CI:0.998 - 3.324)。3093G/3093G和520T/520T基因型是中缅边境附近中国居民中CR1的主要遗传变异,T520C的T等位基因与该地区的疟疾流行率相关。虽然G6PD缺乏不能预防疟疾,但它可能会削弱该人群中疟疾与CR1多态性之间的关联。GTGTGTC单倍型也与该地区的疟疾流行率相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a00d/4616751/16e992f92bdb/medi-94-e1681-g002.jpg

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