KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians
KIR content genotypes associate with carriage of hepatitis B surface antigen, e antigen and HBV viral load in Gambians
复制标题
DOI：
10.1371/journal.pone.0188307
复制
发表时间：
2017-11-17
期刊：
影响因子：
3.7
通讯作者：
Walton, Robert
中科院分区：
文献类型：
--
作者：
Yindom, Louis-Marie;Mendy, Maimuna;Walton, Robert
背景肝细胞癌（HCC）每年在全世界造成超过80万人死亡，主要发生在低收入国家，并且随着B型肝炎（HBV）和C型肝炎（HCV）病毒的传播，在发达国家的发病率迅速上升。自然杀伤（NK）细胞通过杀死由杀伤细胞免疫球蛋白样受体（KIR）识别的异常细胞来防止病毒感染和肿瘤。因此，编码这些受体的基因和单倍型可能在决定初始肝炎感染和随后的慢性肝病和肿瘤形成的结果方面很重要。HBV在冈比亚非常流行，是肝脏疾病的最常见原因。冈比亚肝癌研究是一个匹配的病例对照研究，在1997年9月和2001年1月之间进行，其中肝病病例被确定在三个三级转诊医院，并与门诊对照匹配，没有肝病的临床证据。MethodsWe分型15 KIR基因使用序列特异性引物聚合酶链反应（PCR-SSP）在279名成年冈比亚人，136例肝病（HCC或肝硬化）和143例匹配对照。我们研究了KIR基因型和单倍型对HBV感染的影响以及与肝硬化和HCC的关系。结果KIR A组基因含量单倍型的纯合性与HBsAg携带相关（OR 3.7，95% CI 1.4-10.0），而端粒A基因型（t-AA）与e抗原血症风险降低相关（OR 0.2，95% CI 0.0-0.6）和较低的病毒载量（平均对数病毒载量5.2 vs. 6.9，p（c）= 0.022）。一种新的端粒B基因型（t-ABx 2）含有KIR 3DS 1（这是罕见的，在西非）也与e抗原血症（OR 8.8，95%CI 1.3-60.5）。有没有协会与肝硬化或hcch.ConclusionCertain KIR配置文件可能会促进清除肝炎B表面抗原，而其他易患e抗原携带和高病毒载量。有必要进行更大规模的研究来量化单个KIR基因、单倍型和KIR/HLA组合对长期病毒携带和肝癌风险的影响。KIR状态可能会告知抗病毒治疗，并确定那些并发症风险增加的患者，以加强监测。
BackgroundHepatocellular carcinoma (HCC) causes over 800,000 deaths worldwide annually, mainly in low income countries, and incidence is rising rapidly in the developed world with the spread of hepatitis B (HBV) and C (HCV) viruses. Natural Killer (NK) cells protect against viral infections and tumours by killing abnormal cells recognised by Killer-cell Immunoglobulin-like Receptors (KIR). Thus genes and haplotypes encoding these receptors may be important in determining both outcome of initial hepatitis infection and subsequent chronic liver disease and tumour formation. HBV is highly prevalent in The Gambia and the commonest cause of liver disease. The Gambia Liver Cancer Study was a matched case-control study conducted between September 1997 and January 2001 where cases with liver disease were identified in three tertiary referral hospitals and matched with out-patient controls with no clinical evidence of liver disease.MethodsWe typed 15 KIR genes using the polymerase chain reaction with sequence specific primers (PCR-SSP) in 279 adult Gambians, 136 with liver disease (HCC or Cirrhosis) and 143 matched controls. We investigated effects of KIR genotypes and haplotypes on HBV infection and associations with cirrhosis and HCC.ResultsHomozygosity for KIR group A gene-content haplotype was associated with HBsAg carriage (OR 3.7, 95% CI 1.4-10.0) whilst telomeric A genotype (t-AA) was associated with reduced risk of e antigenaemia (OR 0.2, 95% CI 0.0-0.6) and lower viral loads (mean log viral load 5.2 vs. 6.9, p(c) = 0.022). One novel telomeric B genotype (t-ABx2) containing KIR3DS1 (which is rare in West Africa) was also linked to e antigenaemia (OR 8.8, 95% CI 1.3-60.5).There were no associations with cirrhosis or HCC.ConclusionCertain KIR profiles may promote clearance of hepatitis B surface antigen whilst others predispose to e antigen carriage and high viral load. Larger studies are necessary to quantify the effects of individual KIR genes, haplotypes and KIR/HLA combinations on long-term viral carriage and risk of liver cancer. KIR status could potentially inform antiviral therapy and identify those at increased risk of complications for enhanced surveillance.