Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility.
Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility.
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DOI：
10.1038/ejhg.2009.8
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发表时间：
2009-08
期刊：
影响因子：
--
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中科院分区：
文献类型：
--
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一些证据表明葡萄糖-6-磷酸脱氢酶（G6PD）缺乏与预防严重疟疾有关。早期的报告显示，撒哈拉以南非洲的大多数G6PD缺乏症是由202A/376G G6PD A-等位基因引起的，最近的G6PD缺乏症的关联研究采用基因分型作为确定酶状态的方便方法。然而，进一步的研究表明，其他G6PD缺陷等位基因在西非一些地区相对普遍。为了研究未被识别的等位基因异质性对关联研究的影响，特别是G6PD缺乏和疟疾的研究，我们对2,488名冈比亚严重疟疾儿童和3,875名对照进行了病例对照分析。重度疟疾与202A/376G G6PD A-等位基因单独分析无显著相关性，但将202A/376G与其他缺陷等位基因合并分析显示出保护信号(男性优势比（OR） 0.77, 95% CI 0.62 ~ 0.95， P=0.016；女性单倍型OR 0.71, 95% CI 0.56 ~ 0.89， P=0.004)。我们已经确定968C突变是冈比亚最常见的G6PD A-等位基因。我们的研究结果强调了等位基因异质性的一些后果，特别是I型错误的增加。他们还表明，G6PD缺陷的雄性半合子和雌性杂合子可以免受严重疟疾的侵害。
Several lines of evidence link glucose-6-phosphate dehydrogenase (G6PD) deficiency to protection from severe malaria. Early reports suggested most G6PD deficiency in Sub-Saharan Africa was due to the 202A/376G G6PD A- allele, and recent association studies of G6PD deficiency have employed genotyping as a convenient way to determine enzyme status. However, further work has suggested that other G6PD deficiency alleles are relatively common in some regions of West Africa. To investigate the consequences of unrecognized allelic heterogeneity on association studies, in particular studies of G6PD deficiency and malaria, we performed a case-control analysis of 2,488 Gambian children with severe malaria and 3,875 controls. No significant association was found between severe malaria and the 202A/376G G6PD A- allele when analyzed alone, but pooling 202A/376G with other deficiency alleles revealed the signal of protection (male odds ratio (OR) 0.77, 95% CI 0.62 - 0.95, P=0.016; female haplotypic OR 0.71, 95% CI 0.56 - 0.89, P=0.004). We have identified the 968C mutation as the most common G6PD A- allele in The Gambia. Our results highlight some of the consequences of allelic heterogeneity, particularly increased type I error. They also suggest that G6PD deficient male hemizygotes and female heterozygotes are protected from severe malaria.
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影响因子：
5.1
作者：
Gonzalez, JM;Portillo, MC;Saiz-Jimenez, C
通讯作者：
Saiz-Jimenez, C
影响因子：
15.8
作者：
Guindo A;Fairhurst RM;Doumbo OK;Wellems TE;Diallo DA
通讯作者：
Diallo DA
DOI：
10.1086/596320
发表时间：
2009-02-15
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Clark TG;Diakite M;Auburn S;Campino S;Fry AE;Green A;Richardson A;Small K;Teo YY;Wilson J;Jallow M;Sisay-Joof F;Pinder M;Griffiths MJ;Peshu N;Williams TN;Marsh K;Molyneux ME;Taylor TE;Rockett KA;Kwiatkowski DP
通讯作者：
Kwiatkowski DP
影响因子：
56.9
作者：
Tishkoff, SA;Varkonyi, R;Clark, AG
通讯作者：
Clark, AG
影响因子：
2.4
作者：
SAENZ, GF;CHAVES, M;YOSHIDA, A
通讯作者：
YOSHIDA, A