Raguema N, Gannoun M B A, Zitouni H, Meddeb S, Benletaifa D, Lavoie J L, Almawi W Y, Mahjoub T
Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, 5000 Street Ibn Sina, Monastir, Tunisia; Faculty of Sciences of Bizerte, University of Carthage, 7021 Jarzouna-Bizerte, Tunisia; Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), 900 St-Denis Street, Tour Viger, R08.452, Montréal, Québec H2X 0A9, Canada.
Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, 5000 Street Ibn Sina, Monastir, Tunisia.
Pregnancy Hypertens. 2018 Jan;11:105-110. doi: 10.1016/j.preghy.2018.01.011. Epub 2018 Jan 31.
Interleukin-10 (IL-10) is implicated in several aspects of pregnancy. As genetic predisposition can be involved in the development of preeclampsia, the association between IL-10's promoter region polymorphisms and this pathology has been investigated, although with conflicting results. To date, only a small cohort study (total n = 40) has evaluated this association in the African continent, and none have been conducted in Tunisia. Hence, we evaluated the association between these polymorphisms and the risk of preeclampsia in a large Tunisian cohort.
345 preeclampsia patients and 300 controls were genotyped for the IL-10 promoter region variants -1082A/G, -819C/T and -592A/C using real-time PCR.
Differences in means were determined by Student's t-test, while intergroup significance was assessed by Pearson χ or 2-way ANOVA. Genotypes were tested for Hardy-Weinberg equilibrium (HWE) in the control and cases. Logistic regression analysis was performed in order to determine the odds ratios and 95% confidence intervals associated with the linkage disequilibrium risk.
An increased frequency of the -819 T (minor) allele and the -819 T/T genotype was seen in preeclampsia cases. Also, three-locus haplotype (-1082AG/-819CT/-592AC) analysis identified the ATA haplotype as having a higher incidence in women with preeclampsia (OR = 1.48, 95% CI: 1.03-2.11) and this was confirmed by multivariate regression analysis (OR = 1.65, 95% CI: 1.13-2.43) after controlling for covariates.
We suggest that the IL-10 -819 T/T variant and the ATA haplotype, which are associated with low production of IL 10, represent genetic risk factors for preeclampsia in Tunisian women.
白细胞介素-10(IL-10)与妊娠的多个方面有关。由于遗传易感性可能参与子痫前期的发生发展,因此对IL-10启动子区域多态性与该疾病之间的关联进行了研究,尽管结果相互矛盾。迄今为止,仅有一项小型队列研究(样本总量n = 40)在非洲大陆评估了这种关联,而在突尼斯尚未开展相关研究。因此,我们在一个大型突尼斯队列中评估了这些多态性与子痫前期风险之间的关联。
采用实时聚合酶链反应(PCR)对345例子痫前期患者和300例对照进行IL-10启动子区域变体-1082A/G、-819C/T和-592A/C的基因分型。
采用学生t检验确定均值差异,采用Pearsonχ²检验或双向方差分析评估组间显著性。在对照组和病例组中对基因型进行哈迪-温伯格平衡(HWE)检验。进行逻辑回归分析以确定与连锁不平衡风险相关的比值比和95%置信区间。
子痫前期病例中-819T(次要)等位基因和-819T/T基因型的频率增加。此外,三位点单倍型(-1082AG/-819CT/-592AC)分析确定ATA单倍型在子痫前期女性中的发生率较高(比值比=1.48,95%置信区间:1.03-2.11),在控制协变量后,多因素回归分析证实了这一点(比值比=1.65,95%置信区间:1.13-2.43)。
我们认为,与IL-10低表达相关的IL-10 -819T/T变体和ATA单倍型是突尼斯女性子痫前期的遗传危险因素。