Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease
Targeted next-generation sequencing and fine linkage disequilibrium mapping reveals association of PNPLA3 and PARVB with the severity of nonalcoholic fatty liver disease
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DOI：
10.1038/jhg.2014.17
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发表时间：
2014-05-01
影响因子：
3.5
通讯作者：
Hotta, Kikuko
中科院分区：
文献类型：
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作者：
Kitamoto, Takuya;Kitamoto, Aya;Hotta, Kikuko
含有PNPLA3、SAMM50和PARVB的基因组区域是非酒精性脂肪性肝病（NAFLD）发生和发展的易感位点。为了寻找该区域的所有常见变异，我们通过远程PCR扩增了28例NAFLD患者的基因组DNA，覆盖了整个易感区域，并使用索引多重次世代测序对DNA进行了测序。我们发现了329种变异，包括4种新的变异。对540名NAFLD患者（488名患有非酒精性脂肪性肝炎（NASH）， 52名患有单纯性脂肪变性）和1012名对照受试者进行了包括插入/缺失在内的精细变异定位。HaploView分析显示，PNPLA3、SAMM50和PARVB分别出现了1和2块、3块和4块的连锁不平衡（LD）。与对照组相比，LD区1-4的变化与NAFLD显著相关
The genomic regions containing PNPLA3, SAMM50 and PARVB are susceptibility loci for the development and progression of nonalcoholic fatty liver disease (NAFLD). In order to search for all common variations in this region, we amplified the genomic DNA of 28 NAFLD patients by long-range PCR, covering the entire susceptibility region and sequenced the DNA using indexed multiplex next-generation sequencing. We found 329 variations, including four novel variations. Fine mapping of variations including insertion/deletions was performed for 540 NAFLD patients (488 with nonalcoholic steatohepatitis (NASH) and 52 with simple steatosis) and 1012 control subjects. HaploView analysis showed that linkage disequilibrium (LD) block 1 and 2 occurred in PNPLA3, block 3 in SAMM50 and block 4 in PARVB. Variations in LD blocks 1-4 were significantly associated with NAFLD as compared with control subjects (P