Hepatology and Molecular Medicine Research Groups, Peninsula Medical School, Plymouth, United Kingdom.
J Med Virol. 2015 Jul;87(7):1207-17. doi: 10.1002/jmv.24179. Epub 2015 Apr 23.
HCV is a major cause of liver disease worldwide. IL-12 plays an essential role in the balance of T helper 1 (Th1) differentiation versus a T helper 2 (Th2) driven response from its naïve precursor. Linkage disequilibrium measures the degree to which alleles at two loci are associated and the non-random associations between alleles at two loci. Haplotypes of the three IL-12B loci studied were determined in the patient cases and the normal healthy control subjects. The frequency of the 12 possible IL-12B haplotypes on the 3 loci was determined in subjects heterozygous at only one of the loci within the studied haplotype. Haplotype frequencies were compared between the patient groups and controls (n = 49) to determine if any preferential combination of markers occurred using chi-squared and applying the Bonferroni correction. 45 HCV RNA negative patients; 88 HCV RNA positive patients; and 15 uninfected cases at high risk of HCV infection (EU) were studied. The haplotype "C" SNP of the 3'UTR with the "E" 4 bp deletion of the intron 4 region was in linkage disequilibrium (χ(2) = 45.15, P < 0.001, 95% CL). The haplotype analysis of the insertion allele of the promoter with the deletion allele of the intron 4("E") IL-12B polymorphism showed linkage disequilibrium (χ(2) = 5.64, P = 0.02). Linkage disequilibrium of polymorphisms is reported in the IL-12 gene in patients with HCV infection and contributes to the understanding of patient genotype and expected production of IL-12, responding to infection.
丙型肝炎病毒是全球范围内导致肝脏疾病的主要原因。白细胞介素-12 在辅助性 T 细胞 1（Th1）分化与辅助性 T 细胞 2（Th2）驱动反应的平衡中起着至关重要的作用，其来自于幼稚前体细胞。连锁不平衡衡量两个基因座上的等位基因的关联程度以及两个基因座上的等位基因之间的非随机关联。在患者病例和正常健康对照受试者中确定了研究的三个白细胞介素-12B 基因座的单倍型。在仅在研究的单倍型内的一个基因座上杂合的受试者中确定了三个基因座上的 12 种可能的白细胞介素-12B 单倍型的频率。在患者组和对照组（n=49）之间比较单倍型频率，以确定是否发生了任何偏好性标记物组合，使用卡方检验并应用 Bonferroni 校正。研究了 45 例丙型肝炎病毒 RNA 阴性患者；88 例丙型肝炎病毒 RNA 阳性患者；和 15 例丙型肝炎病毒感染高危（EU）的未感染病例。3'UTR 的“C”SNP 与内含子 4 区域的“E”4bp 缺失的单倍型处于连锁不平衡状态（χ(2)=45.15，P<0.001，95%置信区间）。启动子插入等位基因与内含子 4 缺失等位基因（“E”）白细胞介素-12B 多态性的单倍型分析显示连锁不平衡（χ(2)=5.64，P=0.02）。丙型肝炎病毒感染患者中白细胞介素-12 基因的多态性连锁不平衡，有助于理解患者基因型和预期产生白细胞介素-12，以应对感染。
