Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, United States of America.
PLoS One. 2010 Feb 15;5(2):e9212. doi: 10.1371/journal.pone.0009212.
Human promoter polymorphisms in the chemokine co-receptor 5 gene (CCR5) have been noted for association with mother-to-child transmission of HIV (HIV MTCT) as well as reduced receptor expression in vitro, but have not been clearly associated with CCR5 expression in vivo. Placental expression of CCR5 may be influenced by such polymorphisms as well as other in vivo regulatory factors.
METHODOLOGY/PRINCIPAL FINDINGS: We evaluated the associations between infant CCR5 polymorphisms, measures of maternal infection, and placental expression of CCR5 among mother-infant pairs in Blantyre, Malawi. RNA was extracted from placental tissue and used in multiplex real-time PCR to quantify gene expression. Through linear regression, we observed that CCR5-2554T (beta = -0.67, 95% CI = -1.23, -0.11) and -2132T (beta = -0.75, 95% CI = -0.131, -0.18) were significantly associated with reduced placental expression of CCR5. An incremental increase in CCR5 expression was observed for incremental increases in expression of two heparan sulfate genes involved in viral infection, HS3ST3A1 (beta = 0.27, 95% CI = 0.18, 0.35) and HS3ST3B1 (beta = 0.11, 95% CI = 0.06, 0.18). Among HIV infected mothers, an incremental increase in maternal HIV viral load was also associated with higher CCR5 expression (beta = 0.76, 95% CI = 0.12, 1.39). Maternal HIV status had no overall effect (beta = 0.072, 95% CI = -0.57, -0.72). Higher CCR5 expression was observed for mothers with malaria but was not statistically significant (beta = 0.37, 95% CI = -0.43, 1.18).
CONCLUSIONS/SIGNIFICANCE: These results provide in vivo evidence for genetic and environmental factors involved in the regulation of CCR5 expression in the placenta. Our findings also suggest that the measurement of placental expression of CCR5 alone is not an adequate indicator of the risk of mother-to-child transmission of HIV.
人类趋化因子受体 5 基因（CCR5）中的启动子多态性与 HIV（母婴传播 HIV）以及体外受体表达降低有关，但与体内 CCR5 表达无明显相关性。胎盘 CCR5 的表达可能受到这种多态性以及其他体内调节因子的影响。
方法/主要发现：我们评估了马拉维布兰太尔母婴对中婴儿 CCR5 多态性、母婴感染措施与胎盘 CCR5 表达之间的关系。从胎盘组织中提取 RNA，并用于多重实时 PCR 定量基因表达。通过线性回归，我们观察到 CCR5-2554T（β=-0.67，95%CI=-1.23，-0.11）和-2132T（β=-0.75，95%CI=-0.131，-0.18）与胎盘 CCR5 表达降低显著相关。与参与病毒感染的两种硫酸乙酰肝素基因 HS3ST3A1（β=0.27，95%CI=0.18，0.35）和 HS3ST3B1（β=0.11，95%CI=0.06，0.18）表达的递增增加，CCR5 的表达也观察到递增增加。在感染 HIV 的母亲中，母体 HIV 病毒载量的递增增加也与更高的 CCR5 表达相关（β=0.76，95%CI=0.12，1.39）。母体 HIV 状况对整体没有影响（β=0.072，95%CI=-0.57，-0.72）。疟疾母亲的 CCR5 表达更高，但无统计学意义（β=0.37，95%CI=-0.43，1.18）。
结论/意义：这些结果为胎盘 CCR5 表达调控中涉及的遗传和环境因素提供了体内证据。我们的研究结果还表明，单独测量胎盘 CCR5 的表达并不能充分说明母婴传播 HIV 的风险。
