University of Hawaii Cancer Center, University of Hawaii at Mānoa, Honolulu, Hawaii, United States of America.
Department of Epidemiology and Biostatistics, University of California - San Francisco, San Francisco, California, United States of America.
PLoS One. 2021 Jul 30;16(7):e0249615. doi: 10.1371/journal.pone.0249615. eCollection 2021.
Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
几项研究发现，胰腺脂肪含量较高与不良健康结果（如糖尿病和代谢综合征）之间存在关联，但对胰腺脂肪的遗传贡献的研究有限。这项全基因组关联研究包括 804 名参与者，他们的胰腺脂肪测量值通过 MRI 评估，在种族多样化的多民族队列-肥胖表型研究（MEC-APS）中进行。两种遗传变异达到全基因组显著水平，位于 13 号染色体 q21.2 上的 rs73449607（Beta = -0.67，P = 4.50x10-8）和位于 6 号染色体 q14 上的 rs7996760（Beta = -0.90，P = 4.91x10-8）与胰腺脂肪的对数比例呈负相关。rs73449607 在非裔美国人中最为常见（13%），而 rs79967607 在欧洲裔美国人中最为常见（6%）。rs73449607 还与 2 型糖尿病风险降低相关（OR = 0.95，95%CI = 0.89-1.00，P = 0.047），该研究纳入了大量非欧洲血统参与者（53102 例病例和 193679 例对照），这些参与者来自人口结构基因组学和流行病学（PAGE）研究和糖尿病遗传学复制和荟萃分析（DIAGRAM）。rs73449607 位于 GSX1 和 PLUTO 之间的基因间区域，而 rs79967607 位于 EPM2A 的内含子 1 中。PLUTO 是一种长非编码 RNA，调节其相邻基因 PDX1 的转录，PDX1 控制成熟胰腺中的β细胞功能，EPM2A 编码的蛋白 laforin 在调节糖原产生中起着关键作用。如果得到验证，这些变异可能表明胰腺脂肪存在遗传成分，以及胰腺脂肪和 2 型糖尿病之间存在共同的病因联系。
