Division of Parasitic Diseases and Malaria, Center for Global Health, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
PLoS One. 2013;8(1):e53948. doi: 10.1371/journal.pone.0053948. Epub 2013 Jan 11.
Immunoglobulin (Ig) GM and KM allotypes, genetic markers of γ and κ chains, are associated with humoral immune responsiveness. Previous studies have shown the relationships between GM6-carrying haplotypes and susceptibility to malaria infection in children and adults; however, the role of the genetic markers in placental malaria (PM) infection and PM with HIV co-infection during pregnancy has not been investigated. We examined the relationship between the gene polymorphisms of Ig GM6 and KM allotypes and the risk of PM infection in pregnant women with known HIV status. DNA samples from 728 pregnant women were genotyped for GM6 and KM alleles using polymerase chain reaction-restriction fragment length polymorphism method. Individual GM6 and KM genotypes and the combined GM6 and KM genotypes were assessed in relation to PM in HIV-1 negative and positive women, respectively. There was no significant effect of individual GM6 and KM genotypes on the risk of PM infection in HIV-1 negative and positive women. However, the combination of homozygosity for GM6(+) and KM3 was associated with decreased risk of PM (adjusted OR, 0.25; 95% CI, 0.08-0.8; P = 0.019) in HIV-1 negative women while in HIV-1 positive women the combination of GM6(+/-) with either KM1-3 or KM1 was associated with increased risk of PM infection (adjusted OR, 2.10; 95% CI, 1.18-3.73; P = 0.011). Hardy-Weinberg Equilibrium (HWE) tests further showed an overall significant positive F(is) (indication of deficit in heterozygotes) for GM6 while there was no deviation for KM genotype frequency from HWE in the same population. These findings suggest that the combination of homozygous GM6(+) and KM3 may protect against PM in HIV-1 negative women while the HIV-1 positive women with heterozygous GM6(+/-) combined with KM1-3 or KM1 may be more susceptible to PM infection. The deficit in heterozygotes for GM6 further suggests that GM6 could be under selection likely by malaria infection.
免疫球蛋白（Ig）GM 和 KM 同种型是γ和κ链的遗传标志，与体液免疫反应有关。先前的研究表明 GM6 携带单体型与儿童和成人疟疾感染易感性之间存在关系；然而，遗传标记在胎盘疟疾（PM）感染和 PM 与怀孕期间 HIV 合并感染中的作用尚未得到研究。我们研究了已知 HIV 状态的孕妇中 Ig GM6 和 KM 同种型基因多态性与 PM 感染风险之间的关系。使用聚合酶链反应-限制性片段长度多态性方法对 728 名孕妇的 DNA 样本进行 GM6 和 KM 等位基因的基因分型。分别评估 GM6 和 KM 个体基因型以及 GM6 和 KM 联合基因型与 HIV-1 阴性和阳性妇女 PM 之间的关系。在 HIV-1 阴性和阳性妇女中，GM6 和 KM 个体基因型均未对 PM 感染风险产生显著影响。然而，GM6(+)和 KM3 纯合性与 PM 风险降低相关（调整后的 OR，0.25；95%CI，0.08-0.8；P=0.019）在 HIV-1 阴性女性中，而在 HIV-1 阳性女性中，GM6(+/-)与 KM1-3 或 KM1 的组合与 PM 感染风险增加相关（调整后的 OR，2.10；95%CI，1.18-3.73；P=0.011）。Hardy-Weinberg 平衡（HWE）测试进一步表明 GM6 的总体显著正 F(is)（杂合子不足的指示），而同一人群中 KM 基因型频率未偏离 HWE。这些发现表明，GM6 纯合子 GM6(+)和 KM3 的组合可能在 HIV-1 阴性女性中预防 PM，而 HIV-1 阳性女性中 GM6(+/-)与 KM1-3 或 KM1 的组合可能更容易感染 PM。GM6 杂合子不足进一步表明 GM6 可能受到疟疾感染的选择。
