Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3.
Mitochondrial haplogroup G is associated with nonalcoholic fatty liver disease, while haplogroup A mitigates the effects of PNPLA3.
复制标题
线粒体单倍群 G 与非酒精性脂肪肝相关，而单倍群 A 减轻 PNPLA3 的影响
DOI：
10.1002/edm2.187
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发表时间：
2021-01
影响因子：
--
通讯作者：
Qu S
中科院分区：
文献类型：
--
作者：
Gusdon AM;Hui Y;Chen J;Mathews CE;Qu S
目的线粒体功能障碍在非酒精性脂肪性肝病（NAFLD）的发病机制中起着关键作用。我们假设线粒体DNA（mtDNA）单倍型群影响中国汉族患者NAFLD的风险，并与PNPLA 3基因型相互作用。线粒体基因组扩增重叠片段和测序。采用限制性片段长度多态性分析（RFLP）对655例NAFLD患者和504例对照者进行PNPLA 3rs 738409基因分型。亚单倍群G3在NAFLD患者中更常见（25.8% vs 6.5%）。PNPLA 3CG基因型导致NAFLD的OR为1.66（95%CI 1.25，2.21），GG基因型导致NAFLD的OR为2.33（95%CI 1.72，3.17）。线粒体单倍型A的患者GG基因型的频率显著较高。在单倍型A组患者中，noPNPLA 3基因型与NAFLD风险增加相关（CG：OR 1.17，95%CI 0.55，2.34; GG：OR 1.04，95%CI 0.66，2.65）。排除单倍型A，CG的OR为1.58（95%CI 1.18，2.12），GG的OR为1.81（95%CI 1.30，2.51）。结论单倍型G与NAFLD风险增加有关PNPLA 3GG基因型在编码单倍型A的患者中比例过高，与单倍型A患者的NAFLD风险无关。线粒体遗传学影响NAFLD风险并与PNPLA 3基因型相互作用
ObjectivesMitochondrial dysfunction plays a pivotal role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD). We hypothesized that mitochondrial DNA (mtDNA) haplogroups affect the risk of NAFLD in Han Chinese patients and interact with PNPLA3 genotypes.DesignNAFLD and control patients were recruited from a tertiary care centre. The mitochondrial genome was amplified in overlapping segments and sequenced. Mitochondrial haplogroups were determined using Mitomaster.PNPLA3rs738409 genotyping was performed using restriction fragment length polymorphism analysis.PatientsWe enrolled 655 NAFLD patients and 504 controls.ResultsMore NAFLD patients encoded haplogroup G; odds ratio (OR) 1.85 (95% confidence interval [CI] 1.16, 2.80). Subhaplogroup G3 was present more frequently in NAFLD patients (25.8% vs 6.5%). ThePNPLA3CG genotype resulted in an OR of 1.66 (95% CI 1.25, 2.21), and the GG genotype resulted in an OR of 2.33 (95% CI 1.72, 3.17) for NAFLD. Patients with mitochondrial haplogroup A had a significantly higher frequency of genotype GG. Among patients with haplogroup A, noPNPLA3genotype was associated with increased NAFLD risk (CG: OR 1.17, 95% CI 0.55, 2.34; GG: OR 1.04 95% CI 0.66, 2.65). Excluding haplogroup A, the OR for CG was 1.58 (95% CI 1.18, 2.12), and the OR for GG was 1.81 (95% CI 1.30, 2.51).ConclusionHaplogroup G was associated with an increased risk of NAFLDPNPLA3GG genotype was overrepresented among patients encoding haplogroup A and was not associated with NAFLD risk among haplogroup A patients. Mitochondrial genetics influence NAFLD risk and interact withPNPLA3genotypes.