NAFLD-related gene polymorphisms and all-cause and cause-specific mortality in an Asian population: the Shanghai Changfeng Study
NAFLD-related gene polymorphisms and all-cause and cause-specific mortality in an Asian population: the Shanghai Changfeng Study
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亚洲人群中 NAFLD 相关基因多态性以及全因和特定原因死亡率：上海长风研究
DOI：
10.1111/apt.16772
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发表时间：
2022
影响因子：
7.6
通讯作者：
Xin Gao
中科院分区：
文献类型：
--
作者：
Mingfeng Xia;Shuai Ma;Qingxia Huang;Hailuan Zeng;Jieyu Ge;Wenjie Xu;Qi Wu;Li Wu;Xiaoming Li;Hui Ma;Lingyan Chen;Qian Li;Qiqige Aleteng;Yu Hu;Wanyuan He;Baishen Pan;Hu;ong Lin;Yan Zheng;Sijia Wang;Huiru Tang;Xin Gao
目的研究5581例中国成年人NAFLD危险等位基因对全因死亡率和死因特异性死亡率的影响。方法采用基因分型芯片检测全基因组基因型，采用1H NMR平台检测血清脂蛋白谱。采用定量超声方法测定肝脏脂肪含量（LFC）。结果全基因组关联分析显示PNPLA 3的一系列变异与LFC相关，包括rs738409 C>G变异（P= 8.6 × 10−7）。进一步的分析验证了TM 6SF 2 rs 58542926 C>T和MBOAT 7 rs641738 C>T变异体与NAFLD的关联。在29 425.1人年的随访期间，总死亡率为816/100 000人年，其中299例死亡归因于心血管疾病，85例归因于肝脏疾病。PNPLA 3 rs738409 C>G变异与肝脏特异性死亡率增加（趋势P = 0.034）但心血管死亡率降低（趋势P = 0.047）独立相关。PNPLA 3、TM 6SF 2和MBOAT 7风险等位基因的复合遗传易感性评分对肝脏特异性和心血管死亡率表现出类似的相反影响。此外，发现NAFLD风险等位基因与肥胖对肝脏特异性死亡率的相互作用（P相互作用< 0.05）。结论PNPLA 3 rs738409 C>G变异及其与TM 6SF 2 rs 58542926 C>T和MBOAT 7 rs641738 C>T变异的组合增加了超重/肥胖中国人的肝脏特异性死亡率，但降低了心血管死亡率。
BackgroundThe PNPLA3 and TM6SF2 gene variants have been found to cause NAFLD with a favourable cardiovascular risk profile.AimsTo investigate the effects of the NAFLD risk alleles on the all‐cause and cause‐specific mortality in 5581 Chinese adults.MethodsThe genome‐wide genotypes were detected using a genotyping array and serum lipoprotein profiles were examined using 1H NMR platform. Liver fat content (LFC) was measured using a quantitative ultrasound method. The vital status was determined using official registration data.ResultsGenome‐wide association analysis showed that a series of variants in PNPLA3 were associated with LFC, including rs738409 C>G variant (P= 8.6 × 10−7). Further analyses validated the associations of TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants with NAFLD. During 29 425.1 person‐years of follow‐up, the overall mortality was 816 per 100 000 person‐years, where 299 deaths were attributable to cardiovascular disease and 85 to liver disease. The PNPLA3 rs738409 C>G variant was independently associated with increased liver‐specific mortality (Pfor trend = 0.034) but reduced cardiovascular mortality (Pfor trend = 0.047). A composite genetic‐predisposition score of PNPLA3, TM6SF2, and MBOAT7 risk alleles presented similar opposite effects on liver‐specific and cardiovascular mortality. Moreover, interactions of the NAFLD risk alleles with adiposity for liver‐specific mortality were found (Pinteraction< 0.05). The reduced serum VLDL1 concentration was responsible for the increased liver‐specific mortality related to NAFLD risk alleles.ConclusionThe PNPLA3 rs738409 C>G variant and its combination with TM6SF2 rs58542926 C>T and MBOAT7 rs641738 C>T variants increase liver‐specific mortality but reduce cardiovascular mortality in overweight/obese Chinese.