Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria.
Common variation in the ABO glycosyltransferase is associated with susceptibility to severe Plasmodium falciparum malaria.
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DOI：
10.1093/hmg/ddm331
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发表时间：
2008-02-15
影响因子：
3.5
通讯作者：
Kwiatkowski DP
中科院分区：
文献类型：
--
作者：
Fry AE;Griffiths MJ;Auburn S;Diakite M;Forton JT;Green A;Richardson A;Wilson J;Jallow M;Sisay-Joof F;Pinder M;Peshu N;Williams TN;Marsh K;Molyneux ME;Taylor TE;Rockett KA;Kwiatkowski DP
越来越多的流行病学和分子证据表明，ABO血型影响宿主对恶性疟原虫严重感染的易感性。常见ABO等位基因的高频率意味着，即使易感性上的微小差异也可能对生活在疟疾流行地区的人的健康产生重大影响。我们进行了一项关联研究，首次利用ABO系统背后的关键分子遗传变异，对3个非洲人群中的9000人进行了基因分型。通过基于人群和家庭的检验，我们证明产生功能性ABO酶的等位基因与O型血型的移码缺失相比，患严重疟疾表型(特别是疟疾贫血)的风险更大：病例对照等位基因优势比(OR)1.2，95%可信区间(CI)1.09-1.32，P=0.0003；家族性研究等位基因OR1.19，CI1.08-1.32，P=0.001；合并所有研究的等位基因OR1.18，CI1.11-1.26，P=2×10−7。分析三个家系，我们发现了父母起源效应的提示性证据。母亲而不是父亲的非O单倍型与严重疟疾显著相关(Weinberg的似然比检验，P=0.046)。最后，我们使用HapMap数据展示了ABO基因座上三个主要HapMap群体之间的低Fst区域(−0.001)，这是Fst在9号染色体(~99.5-99.9百分位数)经验分布中的异常值。这种低FST区域可能是ABO基因座长期平衡选择的信号，由包括恶性疟原虫在内的多种感染性病原体引起。
There is growing epidemiological and molecular evidence that ABO blood group affects host susceptibility to severe Plasmodium falciparum infection. The high frequency of common ABO alleles means that even modest differences in susceptibility could have a significant impact on the health of people living in malaria endemic regions. We performed an association study, the first to utilize key molecular genetic variation underlying the ABO system, genotyping >9000 individuals across 3 African populations. Using population- and family-based tests we demonstrated that alleles producing functional ABO enzymes are associated with greater risk of severe malaria phenotypes (particularly malarial anemia) in comparison with the frameshift deletion underlying blood group O: Case-control allelic odds ratio (OR) 1.2, 95% confidence interval (CI) 1.09 – 1.32, P=0.0003; Family-studies allelic OR 1.19, CI 1.08 – 1.32, P=0.001; Pooled across all studies allelic OR 1.18, CI 1.11 - 1.26, P=2×10−7. Analyzing the family trios we found suggestive evidence of a parent-of-origin effect at the ABO locus. Non-O haplotypes inherited from mothers, but not fathers, are significantly associated with severe malaria (likelihood ratio test of Weinberg, P=0.046). Finally we used HapMap data to demonstrate a region of low FST (−0.001) between the three main HapMap population groups across the ABO locus, an outlier in the empirical distribution of FST across chromosome 9 (~99.5 – 99.9th centile). This low FST region may be a signal of longstanding balancing selection at the ABO locus, caused by multiple infectious pathogens including P. falciparum.
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影响因子：
9.8
作者：
Akey JM;Eberle MA;Rieder MJ;Carlson CS;Shriver MD;Nickerson DA;Kruglyak L
通讯作者：
Kruglyak L
影响因子：
3.1
作者：
Barragan, A;Kremsner, PG;Carlson, J
通讯作者：
Carlson, J
影响因子：
5.1
作者：
Gonzalez, JM;Portillo, MC;Saiz-Jimenez, C
通讯作者：
Saiz-Jimenez, C
DOI：
10.1084/jem.176.5.1311
发表时间：
1992-11-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Carlson J;Wahlgren M
通讯作者：
Wahlgren M
影响因子：
2.1
作者：
Dudbridge, F
通讯作者：
Dudbridge, F