Li Yang Fan, Zheng Jing, Peng He Wei, Cai Xiao Lin, Pan Xin Ting, Li Hui Quan, Hong Qi Zhu, Hu Zhi Jian, Wu Yun Li, Peng Xian-E
Department of Epidemiology and Health Statistics, Fujian Provincial Key Laboratory of Environment Factors and Cancer, School of Public Health, Fujian Medical University, Fuzhou, 350108, China.
Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350108, China.
BMC Gastroenterol. 2021 Apr 14;21(1):171. doi: 10.1186/s12876-021-01750-4.
The prevalence of Non-alcoholic fatty liver disease (NAFLD) is increasing and emerging as a global health burden. In addition to environmental factors, numerous studies have shown that genetic factors play an important role in the development of NAFLD. Copy number variation (CNV) as a genetic variation plays an important role in the evaluation of disease susceptibility and genetic differences. The aim of the present study was to assess the contribution of CNV to the evaluation of NAFLD in a Chinese population.
Genome-wide analysis of CNV was performed using high-density comparative genomic hybridisation microarrays (ACGH). To validate the CNV regions, TaqMan real-time quantitative PCR (qPCR) was utilized.
A total of 441 CNVs were identified, including 381 autosomal CNVs and 60 sex chromosome CNVs. By merging overlapping CNVs, a genomic CNV map of NAFLD patients was constructed. A total of 338 autosomal CNVRs were identified, including 275 CNVRs with consistent trends (197 losses and 78 gains) and 63 CNVRs with inconsistent trends. The length of the 338 CNVRs ranged from 5.7 kb to 2.23 Mb, with an average size of 117.44 kb. These CNVRs spanned 39.70 Mb of the genome and accounted for ~ 1.32% of the genome sequence. Through Gene Ontology and genetic pathway analysis, we found evidence that CNVs involving nine genes may be associated with the pathogenesis of NAFLD progression. One of the genes (NLRP4 gene) was selected and verified by quantitative PCR (qPCR) method with large sample size. We found the copy number deletion of NLRP4 was related to the risk of NAFLD.
This study indicate the copy number variation is associated with NAFLD. The copy number deletion of NLRP4 was related to the risk of NAFLD. These results could prove valuable for predicting patients at risk of developing NAFLD.
非酒精性脂肪性肝病（NAFLD）的患病率正在上升，并成为一种全球健康负担。除环境因素外，大量研究表明遗传因素在NAFLD的发生发展中起重要作用。拷贝数变异（CNV）作为一种遗传变异，在疾病易感性评估和遗传差异评估中发挥着重要作用。本研究的目的是评估CNV在中国人群NAFLD评估中的作用。
使用高密度比较基因组杂交微阵列（ACGH）进行全基因组CNV分析。为验证CNV区域，采用TaqMan实时定量PCR（qPCR）。
共鉴定出441个CNV，包括381个常染色体CNV和60个性染色体CNV。通过合并重叠的CNV，构建了NAFLD患者的基因组CNV图谱。共鉴定出338个常染色体CNVR，包括275个趋势一致的CNVR（197个缺失和78个增加）和63个趋势不一致的CNVR。338个CNVR的长度范围为5.7 kb至2.23 Mb，平均大小为117.44 kb。这些CNVR跨越基因组的39.70 Mb，占基因组序列的约1.32%。通过基因本体论和遗传途径分析，我们发现涉及9个基因的CNV可能与NAFLD进展的发病机制有关。选择其中一个基因（NLRP4基因），并通过大样本量的定量PCR（qPCR）方法进行验证。我们发现NLRP4的拷贝数缺失与NAFLD的风险相关。
本研究表明拷贝数变异与NAFLD相关。NLRP4的拷贝数缺失与NAFLD的风险相关。这些结果对于预测有发生NAFLD风险的患者可能具有重要价值。
