Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya.
Genetic variation in CSF2 (5q31.1) is associated with longitudinal susceptibility to pediatric malaria, severe malarial anemia, and all-cause mortality in a high-burden malaria and HIV region of Kenya.
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DOI：
10.1186/s41182-022-00432-5
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发表时间：
2022-06-25
影响因子：
4.5
通讯作者：
中科院分区：
文献类型：
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作者：
恶性疟原虫感染仍然是大流行传播地区发病和死亡的主要原因之一。集落刺激因子 2 基因 (CSF2) 位于 5q31.1 区域内，编码粒细胞-巨噬细胞集落刺激因子 (GM-CSF)，这是一种介导宿主免疫反应的造血生长因子。由于 CSF2 变异对疟疾发病机制的影响尚未报道，我们研究了 CSF2:g-7032 G > A (rs168681:G > A) 和 CSF2:g.64544T > C 侧翼的 5q31.1 基因区域中两个遗传变异的影响(rs246835:T > C) 36 个月随访期间疟疾和严重疟疾贫血 (SMA、Hb < 5.0 g/dL) 发作的发生率和时间。儿童（n = 1654 名，年龄 2-70 个月）是从肯尼亚西部恶性疟原虫大流行传播区招募的。疟疾发病率比 (IRR) 降低是由于 CSF2:g.64544 TC 基因型 (P = 0.0277) 和 CSF2 AC/GC 双倍型 (P = 0.0015) 的遗传所致。在 CSF2 AT/GC 双倍型携带者中观察到疟疾的 IRR 增加 (P = 0.0237)，而 CSF2 AT 单倍型的遗传增加了 SMA 的 IRR (P = 0.0166)。估计疟疾纵向风险的模型显示 CSF2 AC 单倍型携带者的危险率降低 (P = 0.0045)。全因死亡率调查显示，CSF2:g-7032 的 GA 基因型遗传会增加死亡风险（P = 0.0315）。年幼儿童（P < 0.0001 和 P = 0.0015）、HIV-1（+）个体（P < 0.0001 和 P < 0.0001）以及 HbSS 携带者（P = 0.0342 和 P = 0.0342）中观察到 SMA 和全因死亡风险较高。 P = 0.0019）。该恶性疟原虫全地方性流行地区的结果表明，基因区域 5q31.1 的变异会影响对疟疾、SMA 和死亡率的易感性，年龄、HIV-1 状态和 HbSS 遗传也是如此。
Plasmodium falciparum infections remain among the leading causes of morbidity and mortality in holoendemic transmission areas. Located within region 5q31.1, the colony-stimulating factor 2 gene (CSF2) encodes granulocyte–macrophage colony-stimulating factor (GM-CSF), a hematopoietic growth factor that mediates host immune responses. Since the effect of CSF2 variation on malaria pathogenesis remains unreported, we investigated the impact of two genetic variants in the 5q31.1 gene region flanking CSF2:g-7032 G > A (rs168681:G > A) and CSF2:g.64544T > C (rs246835:T > C) on the rate and timing of malaria and severe malarial anemia (SMA, Hb < 5.0 g/dL) episodes over 36 months of follow-up. Children (n = 1654, aged 2–70 months) were recruited from a holoendemic P. falciparum transmission area of western Kenya. Decreased incidence rate ratio (IRR) for malaria was conferred by inheritance of the CSF2:g.64544 TC genotype (P = 0.0277) and CSF2 AC/GC diplotype (P = 0.0015). Increased IRR for malaria was observed in carriers of the CSF2 AT/GC diplotype (P = 0.0237), while the inheritance of the CSF2 AT haplotype increased the IRR for SMA (P = 0.0166). A model estimating the longitudinal risk of malaria showed decreased hazard rates among CSF2 AC haplotype carriers (P = 0.0045). Investigation of all-cause mortality revealed that inheritance of the GA genotype at CSF2:g-7032 increased the risk of mortality (P = 0.0315). Higher risk of SMA and all-cause mortality were observed in younger children (P < 0.0001 and P = 0.0015), HIV-1(+) individuals (P < 0.0001 and P < 0.0001), and carriers of HbSS (P = 0.0342 and P = 0.0019). Results from this holoendemic P. falciparum area show that variation in gene region 5q31.1 influences susceptibility to malaria, SMA, and mortality, as does age, HIV-1 status, and inheritance of HbSS.
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影响因子：
3.7
作者：
Cotterchio M;Lowcock E;Bider-Canfield Z;Lemire M;Greenwood C;Gallinger S;Hudson T
通讯作者：
Hudson T
影响因子：
12.8
作者：
Hong IS
通讯作者：
Hong IS
影响因子：
6.6
作者：
Katsura A;Tamura Y;Hokari S;Harada M;Morikawa M;Sakurai T;Takahashi K;Mizutani A;Nishida J;Yokoyama Y;Morishita Y;Murakami T;Ehata S;Miyazono K;Koinuma D
通讯作者：
Koinuma D
DOI：
10.1158/1055-9965.epi-10-0779
发表时间：
2011-01
期刊：
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子：
--
作者：
Johnson LG;Schwartz SM;Malkki M;Du Q;Petersdorf EW;Galloway DA;Madeleine MM
通讯作者：
Madeleine MM
影响因子：
3
作者：
Amek, Nyaguara O.;Van Eijk, Annemieke;Vounatsou, Penelope
通讯作者：
Vounatsou, Penelope