Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus
Influence of the rs738409 polymorphism in patatin-like phospholipase 3 on the treatment efficacy of non-alcoholic fatty liver disease with type 2 diabetes mellitus
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DOI：
10.1111/hepr.12552
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发表时间：
2016-03-01
影响因子：
4.2
通讯作者：
Chayama, Kazuaki
中科院分区：
文献类型：
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作者：
Kan, Hiromi;Hyogo, Hideyuki;Chayama, Kazuaki
AimA全基因组关联研究显示patatin样磷脂酶3基因（PNPLA 3）rs738409单核苷酸多态性（SNP）与非酒精性脂肪肝（NAFLD）密切相关。最近的初步研究调查了二肽基肽酶-4抑制剂对NAFLD合并2型糖尿病（DM）患者肝功能和葡萄糖代谢的影响。我们在此评估了阿格列汀在NAFLD患者2型糖尿病以及基因型之间的关系rs738409在PNPLA 3和治疗effictiveness. MethodsForty 1活检证实NAFLD患者2型糖尿病治疗25毫克/天阿格列汀的疗效进行了回顾性登记。PNPLA 3的rs738409位点在所有患者中均存在。结果治疗前后平均糖化血红蛋白（HbA 1c）水平基本保持不变。此外，在随访期间未观察到天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）水平的显著变化。观察到HbA 1c（HbA 1c）水平的改善与AST（AST）和ALT（ALT）水平的变化呈正相关（r分别为0.325和0.439）。携带危险等位基因（G-等位基因）的患者HbA 1c与转氨酶变化呈正相关。此外，总胆固醇，甘油三酯和透明质酸的水平的改善显着更大的G-等位基因患者在weight loss group.ConclusionThe治疗NAFLD与2型DM阿格列汀有助于改善NAFLD。我们的研究结果表明，PNPLA 3危险等位基因的差异影响了这种治疗的疗效。
AimA genome-wide association study revealed that the single nucleotide polymorphism (SNP) rs738409 in the patatin-like phospholipase 3 gene (PNPLA3) was strongly associated with non-alcoholic fatty liver disease (NAFLD). Recent pilot studies investigated the effects of dipeptidyl peptidase-4 inhibitors on liver function and glucose metabolism in NAFLD with type 2 diabetes mellitus (DM). We herein evaluated the efficacy of alogliptin in NAFLD patients with type 2 DM as well as the relationship between genotypes at rs738409 in PNPLA3 and treatment efficacy.MethodsForty-one biopsy-proven NAFLD patients with type 2 DM treated with 25mg/day alogliptin were retrospectively enrolled. SNP rs738409 in PNPLA3 was present in all patients. Clinical data were measured before and after the treatment.ResultsAverage hemoglobin A1c (HbA1c) levels mostly remained unchanged. Moreover, significant changes were not noted in the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) during the follow-up period. A positive correlation was observed between improvements in HbA1c (HbA1c) levels and changes in AST (AST) and ALT (ALT) levels (r=0.325 and 0.439, respectively). Patients with the risk allele (G-allele) showed more positive correlation between HbA1c and changes in transaminase. Furthermore, improvements in the levels of total cholesterol, triglycerides and hyaluronic acid were significantly greater in G-allele patients in the weight loss group.ConclusionThe treatment of NAFLD with type 2 DM with alogliptin contributed to the amelioration of NAFLD. Our results suggested that differences in the PNPLA3 risk allele affected the therapeutic effects of this treatment.