Replication analysis of genetic association of the NCAN-CILP2 region with plasma lipid levels and non-alcoholic fatty liver disease in Asian and Pacific ethnic groups.
Replication analysis of genetic association of the NCAN-CILP2 region with plasma lipid levels and non-alcoholic fatty liver disease in Asian and Pacific ethnic groups.
复制标题
DOI：
10.1186/s12944-016-0181-z
复制
发表时间：
2016-01-13
影响因子：
4.5
通讯作者：
Iwamoto S
中科院分区：
文献类型：
--
作者：
Boonvisut S;Nakayama K;Makishima S;Watanabe K;Miyashita H;Lkhagvasuren M;Kagawa Y;Iwamoto S
Neurocan-软骨中间层蛋白2（NCAN-CILP 2）区域形成紧密连锁不平衡（LD）阻断，并且与欧洲血统个体中的血浆脂质水平和非酒精性脂肪性肝病（NAFLD）相关，但在马来人和日本人族群中不相关。最近的全基因组重测序研究确定了跨膜6超家族成员2（TM 6SF 2）基因的错义单核苷酸多态性（SNP）（rs 58542926），该基因位于与肝脏甘油三酯含量相关的NCAN-CILP 2区域。本研究旨在分析该地区SNPs对亚洲和太平洋地区种族人群NAFLD和血脂水平的影响，并揭示依赖于种族的积极和消极遗传关联背后的原因。样本和特征数据收集自3，013名日本人，119名帕劳人，947名蒙古人，212名泰国人和401名中国人。肝脏超声检查数据来自日本个体。使用5个SNPs的基因分型数据，rs 58542926，rs735273，rs 1009136，rs 1858999和rs 16996148，通过多元线性回归验证对血脂水平的影响，并通过logistic回归分析检查与日本人群NAFLD的关联。rs 58542926与日本（P = 0.0009，效应量= 9.5（±3.25）mg/dl/等位基因）和泰国（P = 0.0008，效应量= 31.6（±11.7）mg/dl/等位基因）研究受试者的血浆甘油三酯（TG）水平显著相关。在蒙古族个体中，rs 58542926与总胆固醇水平显着相关（P = 0.0003，11.7（±3.2）mg/dl/等位基因），但与TG水平无关。在中国个体的多重比较中，rs 58542926与TG水平弱相关（P = 0.022），尽管未达到统计学显著性阈值。在帕劳人中，与所研究的SNP没有显著关联。rs 58542926也显示与日本NAFLD显著相关。次要等位基因（t）增加NAFLD风险（OR 1.682，95% CI 1.289-2.196，p值0.00013）。该研究证实了TM 6SF 2的错义SNP rs 58542926与多个东亚种族群体的血脂水平以及日本个体的NAFLD的遗传关联。
The Neurocan-cartilage intermediate layer protein 2 (NCAN-CILP2) region forms a tight linkage disequilibrium (LD) block and is associated with plasma lipid levels and non-alcoholic fatty liver disease (NAFLD) in individuals of European descent but not in the Malay and Japanese ethnic groups. Recent genome-wide resequence studies identified a missense single-nucleotide polymorphism (SNP) (rs58542926) of the transmembrane 6 superfamily member 2 (TM6SF2) gene in the NCAN-CILP2 region related to hepatic triglyceride content. This study aims to analyze the influences of SNPs in this region on NAFLD and plasma lipid levels in the Asian and Pacific ethnic groups and to reveal the reasons behind positive and negative genetic associations dependent on ethnicity. Samples and characteristic data were collected from 3,013 Japanese, 119 Palauan, 947 Mongolian, 212 Thai and 401 Chinese people. Hepatic sonography data was obtained from the Japanese individuals. Genotyping data of five SNPs, rs58542926, rs735273, rs1009136, rs1858999, and rs16996148, were used to verify the effect on serum lipid levels by multiple linear regression, and the association with NAFLD in the Japanese population was examined by logistic regression analysis. rs58542926 showed significant association with the plasma triglyceride (TG) level in Japanese (P = 0.0009, effect size = 9.5 (±3.25) mg/dl/allele) and Thai (P = 0.0008, effect size = 31.6 (±11.7) mg/dl/allele) study subjects. In Mongolian individuals, there was a significant association of rs58542926 with total cholesterol level (P = 0.0003, 11.7 (±3.2) mg/dl/allele) but not with TG level. In multiple comparisons in Chinese individuals, rs58542926 was weakly (P = 0.022) associated with TG levels, although the threshold for statistical significance was not reached. In Palauan individuals, there was no significant association with the studied SNPs. rs58542926 also showed significant association with Japanese NAFLD. The minor allele (t) increased NAFLD risk (OR 1.682, 95 % CI 1.289–2.196, p value 0.00013). This study confirmed the genetic association of missense SNP of TM6SF2, rs58542926, with plasma lipid levels in multiple East Asian ethnic groups and with NAFLD in Japanese individuals.