微小RNA-146a rs2910164与接受高效抗逆转录病毒治疗的南非黑人女性严重先兆子痫有关。
MicroRNA-146a rs2910164 is associated with severe preeclampsia in Black South African women on HAART.
作者信息
Maharaj Niren Ray, Ramkaran Prithiksha, Pillay Siddharthiya, Chuturgoon Anil Amichund
机构信息
Department of Obstetrics and Gynaecology, Prince Mshiyeni Memorial Hospital, Durban, South Africa.
Discipline of Medical Biochemistry and Chemical Pathology, School of Laboratory Medicine and Medical Sciences, College of Health Sciences, University of KwaZulu-Natal, Howard College Campus, George Campbell Building-South Entrance, 3rd Floor, King George V Avenue, Durban, South Africa.
出版信息
BMC Genet. 2017 Jan 19;18(1):5. doi: 10.1186/s12863-016-0469-z.
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
南非黑人女性中先兆子痫和艾滋病毒的患病率较高，这两种情况都与炎症增加有关。miR-146a是一种与炎症相关的微小RNA，一种常见的单核苷酸多态性（rs2910164）与多种疾病状况相关。迄今为止，尚未在南非黑人女性中对该单核苷酸多态性进行研究。因此，我们旨在研究患先兆子痫的南非黑人中miR-146a G>C单核苷酸多态性，并进一步研究接受高效抗逆转录病毒治疗（HAART）的先兆子痫（PE）合并艾滋病毒感染女性之间可能存在的关联。
方法
这项基于医院的病例对照研究纳入了95名血压正常的和98名患先兆子痫的南非黑人女性（年龄在16 - 46岁之间）。通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对患者和对照进行基因分型。使用细胞计数珠阵列分析，测定了4组孕妇的血清细胞因子水平（包括与Th1和Th2相关的细胞因子），即：血压正常者、艾滋病毒感染者;先兆子痫合并艾滋病毒感染者以及先兆子痫患者。
结果
在我们的数据中，miR-146a多态性与先兆子痫易感性之间没有显著关联。然而，在亚组分析中，变异基因型（GC/CC）与较低的重度先兆子痫风险显著相关（p = 0.0497），在合并艾滋病毒感染及接受HAART的情况下更是如此（p = 0.017）。在血压正常组中，变异基因型与较低的白细胞介素-2水平相关，在整个血压正常组（269±1.26（36）对273±1.31（23）；p = 0.035）以及先兆子痫合并艾滋病毒感染亚组（265±1.54（19）对271±1.38（11）；p = 0.008）中均如此。
结论
我们的研究表明，miR-146a rs2910164多态性可能与先兆子痫易感性、细胞因子或相关特征无关。然而，miR-146a GC/CC基因型可能会降低患重度先兆子痫的易感性，这可能会受到接受HAART的孕妇中合并艾滋病毒感染情况的进一步影响。这种变异基因型也可能与循环白细胞介素-2水平降低有关，从而降低血压正常女性的促炎反应，这可能会受到艾滋病毒感染和HAART的进一步影响。
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