BACKGROUND & AIMS:
BACKGROUND:South African (SA) Black women have a high prevalence of preeclampsia and HIV, both conditions associated with increased inflammation. miR-146a is an inflammatory-associated miR and a common single nucleotide polymorphism (rs2910164) has been associated with several disease conditions. To date, this SNP has not been investigated in SA Black women. We therefore aimed to investigate the miR-146a G > C SNP in SA Blacks with preeclampsia, and further examine possible association among preeclamptic (PE) women with HIV infection on HAART.
METHODS:This hospital-based, case-control study included 95 normotensive and 98 PE Black SA women (aged 16-46 years old). Patients and controls were genotyped by PCR-RFLP. Using a Cytometric Bead Array assay, serum cytokine levels (including Th1- and Th2-related cytokines) were determined in 4 groups of pregnant women, viz: normotensive, HIV infected, PE + HIV infected, and PE women.
RESULTS:There was no significant association between the miR-146a polymorphism and PE susceptibility in our data. However, in the subgroup analyses, the variant genotypes (GC/CC) were significantly associated with lower severe PE risk (p = 0.0497), more especially in the presence of HIV and HAART (p = 0.017). In the normotensive group, the variant genotypes were associated with lower IL-2 in both the total normotensive group (269 ± 1.26 (36) vs 273 ± 1.31 (23); p = 0.035) and the PE HIV+ sub-group 265 ± 1.54 (19) vs 271 ± 1.38 (11); p = 0.008).
CONCLUSIONS:Our study suggests that miR-146a rs2910164 polymorphism might not be associated with PE susceptibility, cytokines or related features. However, the miR-146a GC/CC genotype might reduce susceptibility to severe PE, which might be further influenced by the presence of co-morbid HIV infection among pregnant women on HAART. This variant genotype may also be associated with reduced circulating IL-2 levels and thus reduced pro-inflammatory response in normotensive women, which may be further influenced by the presence of HIV infection and HAART.
背景与目标:
背景:南非黑人妇女患有先兆子痫和艾滋病毒,这两种情况都与炎症增加有关。 miR-146a是一种与炎症相关的miR,常见的单核苷酸多态性(rs2910164)与多种疾病相关。迄今为止,尚未在SA黑人妇女中对该SNP进行过调查。因此,我们旨在调查子痫前期黑人中的miR-146a G> C SNP,并进一步检查子痫前期(PE)妇女在HAART上感染HIV的可能关联。
方法:这项基于医院的病例对照研究包括95名血压正常和98名PE Black SA妇女(年龄16-46岁)。通过PCR-RFLP对患者和对照进行基因分型。使用细胞计数珠阵列测定法,确定了4组孕妇的血清细胞因子水平(包括Th1和Th2相关的细胞因子),即血压正常,HIV感染,PE 3 + HIV感染和PE妇女。
结果:在我们的数据中,miR-146a多态性与PE易感性之间没有显着关联。然而,在亚组分析中,变异基因型(GC / CC)与较低的严重PE风险显着相关(p = 0.0497),尤其是在存在HIV和HAART的情况下(p = 0.017)。在血压正常组中,总血压正常组中的变异基因型与较低的IL-2相关(269±±1.26(36)vs 273±±1.31(23); p = 0.035)和PE HIV亚组265±1.54 (19)vs 271±1.38(11); p = 0.008)。
结论:我们的研究表明,miR-146a rs2910164多态性可能与PE易感性,细胞因子或相关特征无关。但是,miR-146a GC / CC基因型可能会降低对严重PE的易感性,这可能进一步受到HAART孕妇中合并感染HIV的感染的影响。这种变异的基因型也可能与循环中的IL-2水平降低有关,从而降低了血压正常女性的促炎反应,这可能进一步受到HIV感染和HAART的影响。