Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Shanghai Jiao Tong University, Shanghai 200030, China.
Shanghai Innovation Center of TCM Health Service, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
Aging (Albany NY). 2022 Mar 25;14(6):2736-2747. doi: 10.18632/aging.203970.
Accumulated studies have pointed out the striking association between variants in or near , , , and nonalcoholic fatty liver disease (NAFLD) at various ages from multiple ethnic groups. This association remained unclear in the Chinese Han elderly population, and whether this relationship correlated to any clinical parameters was also unclear.
This study aims to decipher the complex relevance between gene polymorphisms, clinical parameters, and NAFLD by association study and mediation analysis.
Eight SNPs (rs2854116, rs2854117, rs780093, rs780094, rs1260362, rs738409, rs2294918, and rs2281135) within , and were genotyped using the MassARRAY® platform in a large Chinese Han sample comprising of 733 elderly NAFLD patients and 824 age- and ethnic-matched controls. Association and mediation analysis were employed by R.
The genotypic frequencies of rs1260326 and rs780094 were significantly different between NAFLD and control (rs1260326: =0.004, =0.020, OR [95%CI]= 0.69 [0.54-0.89]; rs780094: =0.005, =0.025, OR [95%CI]= 0.70 [0.55-0.90]). Particularly, an increased triglyceride level was observed in carriers of rs1260326 T allele (1.94±1.19 mmol/L) compared with non-carriers (1.73±1.05 mmol/L).no significant results were observed in rs780094. Notably, triglyceride levels had considerably indirect impacts on association between NAFLD and rs1260326 (β =0.01, 95% CI: 0.01-0.02), indicating that 12.7% of the association of NAFLD with rs1260326 was mediated by triglyceride levels.
Our results identified a prominent relationship between rs1260326 and NAFLD, and highlighted the mediated effect of triglyceride levels on the that association in the Chinese Han elderly.
大量研究指出，在来自多个种族的不同年龄段人群中，变体或附近的变体与非酒精性脂肪性肝病（NAFLD）之间存在显著关联。这种关联在汉族老年人群中尚不清楚，这种关系是否与任何临床参数相关也不清楚。
本研究旨在通过关联研究和中介分析来破译基因多态性、临床参数与 NAFLD 之间的复杂相关性。
采用 MassARRAY®平台对 8 个位于 、和中的 SNP（rs2854116、rs2854117、rs780093、rs780094、rs1260362、rs738409、rs2294918 和 rs2281135）在一个包含 733 名汉族老年 NAFLD 患者和 824 名年龄和种族匹配对照的大型汉族样本中进行基因分型。采用 R 进行关联和中介分析。
rs1260326 和 rs780094 的基因型频率在 NAFLD 和对照组之间存在显著差异（rs1260326：=0.004，=0.020，OR[95%CI]=0.69[0.54-0.89]；rs780094：=0.005，=0.025，OR[95%CI]=0.70[0.55-0.90]）。特别是，与非携带者相比，rs1260326 T 等位基因携带者的甘油三酯水平升高（1.94±1.19mmol/L）（1.73±1.05mmol/L）。rs780094 未观察到显著结果。值得注意的是，甘油三酯水平对 NAFLD 与 rs1260326 之间的关联具有显著的间接影响（β=0.01，95%CI：0.01-0.02），表明 NAFLD 与 rs1260326 之间 12.7%的关联是由甘油三酯水平介导的。
我们的研究结果确定了 rs1260326 与 NAFLD 之间的显著关系，并强调了甘油三酯水平对这种关联的中介作用。
