Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.
Genetic variants in COL13A1, ADIPOQ and SAMM50, in addition to the PNPLA3 gene, confer susceptibility to elevated transaminase levels in an admixed Mexican population.
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DOI：
10.1016/j.yexmp.2018.01.001
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发表时间：
2018-03
影响因子：
3.6
通讯作者：
Velázquez-Cruz R
中科院分区：
文献类型：
--
作者：
Larrieta-Carrasco E;Flores YN;Macías-Kauffer LR;Ramírez-Palacios P;Quiterio M;Ramírez-Salazar EG;León-Mimila P;Rivera-Paredez B;Cabrera-Álvarez G;Canizales-Quinteros S;Zhang ZF;López-Pérez TV;Salmerón J;Velázquez-Cruz R
非酒精性脂肪性肝病（NAFLD）是指非酒精引起的肝细胞中多余脂肪的积累。转氨酶水平升高是肝脏疾病的常见指标，包括NAFLD。先前，我们证明PNPLA 3（rs738409），LYPLAL 1（rs 12137855），PPP 1 R3 B（rs 4240624）和GCKR（rs780094）与超重/肥胖墨西哥成年人转氨酶水平升高相关。我们研究了在全基因组关联研究中鉴定的288个SNP与178例NAFLD和454例健康对照的墨西哥-梅斯蒂索混合样本中转氨酶水平升高风险之间的关联。PNPLA 3中的rs 2896019、rs 12483959和rs3810622 SNP以及COL 13 A1中的rs 1227756与丙氨酸氨基转移酶（ALT，≥40 IU/L）升高相关。基于ADIPOQ、COL 13 A1、PNPLA 3和SAMM 50基因中6个SNP的多基因风险评分（PRS）也与ALT升高相关。携带9-12个危险等位基因的个体的ALT和AST水平分别比携带1-4个危险等位基因的个体高65.8%和48.5%。PRS显示ALT水平升高的风险最大，其显著性水平高于个体变异。我们的研究结果表明，COL 13 A1，ADIPOQ，SAMM 50和PNPLA 3的变异与墨西哥混合血统成年人NAFLD/转氨酶水平升高的风险之间存在显着关联。这是第一个研究高密度单核苷酸筛查墨西哥混血人口的遗传变异。这些变化对拉丁裔人群NAFLD发展和进展的影响程度需要进一步分析。
Non-alcoholic fatty liver disease (NAFLD) is the accumulation of extra fat in liver cells not caused by alcohol. Elevated transaminase levels are common indicators of liver disease, including NAFLD. Previously, we demonstrated that PNPLA3 (rs738409), LYPLAL1 (rs12137855), PPP1R3B (rs4240624), and GCKR (rs780094) are associated with elevated transaminase levels in overweight/obese Mexican adults. We investigated the association between 288 SNPs identified in genome-wide association studies and risk of elevated transaminase levels in an admixed Mexican-Mestizo sample of 178 cases of NAFLD and 454 healthy controls. The rs2896019, rs12483959, and rs3810622 SNPs in PNPLA3 and rs1227756 in COL13A1 were associated with elevated alanine aminotransferase (ALT, ≥40 IU/L). A polygenic risk score (PRS) based on six SNPs in the ADIPOQ, COL13A1, PNPLA3, and SAMM50 genes was also associated with elevated ALT. Individuals carrying 9–12 risk alleles had 65.8% and 48.5% higher ALT and aspartate aminotransferase (AST) levels, respectively, than those with 1–4 risk alleles. The PRS showed the greatest risk of elevated ALT levels, with a higher level of significance than the individual variants. Our findings suggest a significant association between variants in COL13A1, ADIPOQ, SAMM50, and PNPLA3, and risk of NAFLD/elevated transaminase levels in Mexican adults with an admixed ancestry. This is the first study to examine high-density single nucleotide screening for genetic variations in a Mexican-Mestizo population. The extent of the effect of these variations on the development and progression of NAFLD in Latino populations requires further analysis.
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影响因子：
24.5
作者：
Kechagias S;Ernersson A;Dahlqvist O;Lundberg P;Lindström T;Nystrom FH;Fast Food Study Group
通讯作者：
Fast Food Study Group
影响因子：
3.9
作者：
Kosoy, Roman;Nassir, Rami;Tian, Chao;White, Phoebe A.;Butler, Lesley M.;Silva, Gabriel;Kittles, Rick;Alarcon-Riquelme, Marta E.;Gregersen, Peter K.;Belmont, John W.;De La Vega, Francisco M.;Seldin, Michael F.
通讯作者：
Seldin, Michael F.
影响因子：
14.8
作者：
Clarke, Geraldine M.;Anderson, Carl A.;Pettersson, Fredrik H.;Cardon, Lon R.;Morris, Andrew P.;Zondervan, Krina T.
通讯作者：
Zondervan, Krina T.
影响因子：
29.4
作者：
Chalasani N;Guo X;Loomba R;Goodarzi MO;Haritunians T;Kwon S;Cui J;Taylor KD;Wilson L;Cummings OW;Chen YD;Rotter JI;Nonalcoholic Steatohepatitis Clinical Research Network
通讯作者：
Nonalcoholic Steatohepatitis Clinical Research Network
脂肪酸蛋白酶基因的常见变体会影响肝酶值。
影响因子：
4
作者：
Kollerits B;Coassin S;Kiechl S;Hunt SC;Paulweber B;Willeit J;Brandstätter A;Lamina C;Adams TD;Kronenberg F
通讯作者：
Kronenberg F