Cunha Luciana Rodrigues da, Vieira Diego Alves, Giampietro Yala Gramigna, Gomes Adriana Dias, Lopes de Faria César Lúcio, Freire de Melo Fabrício, Teixeira Rosângela, Teixeira de Carvalho Andrea, Oliveira Luciana Maria, Filho Olindo Assis Martins, Rocha Gifone Aguiar, Maria de Magalhães Queiroz Dulciene, Neves Fernando Silva, Silva Luciana Diniz
Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil; Neurosciences Post-Graduate Programme, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Outpatient Clinic of Viral Hepatitis, Instituto Alfa de Gastroenterologia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil.
Clin Res Hepatol Gastroenterol. 2019 Aug;43(4):417-426. doi: 10.1016/j.clinre.2018.11.015. Epub 2018 Dec 24.
To investigate the association of IL10 SNPs in chronic hepatitis C (CHC) patients with and without the first major depressive episode (MDE), as well as their association with plasma levels of target cytokines.
A hundred and thirty two CHC patients (32 with and 100 without first MDE) and 98 controls were prospectively enrolled in this cross-sectional study. MDE was diagnosed by a psychiatrist, using the Mini International Neuropsychiatric Interview Plus 5.0. IL10 polymorphisms (-1082 G/A, -819C/T and -592C/A IL10 SNPs) were evaluated by Taqman SNP genotyping assay. Plasma concentrations of IL-2, IL-6, IL-10, IFN-γ and TNF-α were determined using the Human Th1/Th2 Cytometric Bead Array kit. The associations were investigated by logistic models.
The frequencies of the studied IL10 SNPs did not differ between the CHC patients and controls. The first MDE was positive and independently associated with the IL10-1082A, IL10-819T and IL10-592*A (ATA) low producer haplotype (OR = 1.50; 95% CI = 1.11-2.04; P = 0.009) and current alcohol misuse (OR = 4.29; 95% CI = 1.22-15.05; P = 0.02), and inversely associated with increasing age (OR = 0.94; 95% CI = 0.91-0.98; P = 0.006). In addition, plasma level of TNF-α was significantly higher in the carriers than in the non-carriers of the IL10 ATA haplotype in patients with the first MDE. The IL-10 and IL-2 plasma levels were significantly higher in the carriers than in non-carriers of the IL10 GCC high producer haplotype, demonstrating the functionality of the studied IL10 polymorphisms.
This is the first study to demonstrate that the IL10 low producer ATA haplotype is associated with the first MDE in patients with CHC.
研究慢性丙型肝炎（CHC）患者中有无首次重度抑郁发作（MDE）与白细胞介素10（IL10）单核苷酸多态性（SNP）的关联，以及它们与血浆中目标细胞因子水平的关联。
本横断面研究前瞻性纳入了132例CHC患者（32例有首次MDE，100例无首次MDE）和98例对照。由精神科医生使用迷你国际神经精神访谈升级版5.0诊断MDE。通过Taqman SNP基因分型检测评估IL10基因多态性（-1082G/A、-819C/T和-592C/A IL10 SNP）。使用人Th1/Th2细胞计数微珠阵列试剂盒测定血浆中白细胞介素-2（IL-2）、白细胞介素-6（IL-6）、白细胞介素-10（IL-10）、干扰素-γ（IFN-γ）和肿瘤坏死因子-α（TNF-α）的浓度。通过逻辑模型研究这些关联。
CHC患者和对照之间所研究的IL10 SNP频率无差异。首次MDE呈阳性且与IL10 -1082A、IL10 -819T和IL10 -592*A（ATA）低产生单倍型独立相关（比值比[OR]=1.50；95%置信区间[CI]=1.11 - 2.04；P=0.009）以及当前酒精滥用（OR=4.29；95% CI=1.22 - 15.05；P=0.02），并与年龄增长呈负相关（OR=0.94；95% CI=0.91 - 0.98；P= 0.006）。此外，在有首次MDE的患者中，IL10 ATA单倍型携带者的血浆TNF-α水平显著高于非携带者。IL10 GCC高产生单倍型携带者的血浆IL-10和IL-2水平显著高于非携带者，证明了所研究的IL10基因多态性的功能性。
这是第一项证明IL10低产生ATA单倍型与CHC患者首次MDE相关的研究。
