Muller Yunhua L, Hanson Robert L, Wiessner Gregory, Nieboer Lori, Kobes Sayuko, Piaggi Paolo, Abdussamad Mahdi, Okani Chidinma, Knowler William C, Bogardus Clifton, Baier Leslie J
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes Of Health, Phoenix, Arizona, USA.
Obesity (Silver Spring). 2015 Oct;23(10):1960-5. doi: 10.1002/oby.21236. Epub 2015 Sep 4.
A prior genome-wide association study (GWAS) in Pima Indians identified variation within FOXO1A that modestly associated with early-onset (onset age < 25 years) type 2 diabetes (T2D). FOXO1A encodes the forkhead transcription factor involved in pancreatic β-cell growth and hypothalamic energy balance; therefore, FOXO1A was analyzed as a candidate gene for T2D and obesity in a population-based sample of 7,710 American Indians.
Tag SNPs in/near FOXO1A (minor allele frequency ≥ 0.05) were analyzed for association with T2D at early onset (n = 1,060) and all ages (n = 7,710) and with insulin secretion (n = 298). SNPs were also analyzed for association with maximum body mass index (BMI) in adulthood (n = 5,918), maximum BMI z-score in childhood (n = 5,350), and % body fat (n = 555).
An intronic SNP rs2297627 associated with early-onset T2D [OR = 1.34 (1.13-1.58), P = 8.7 × 10(-4)] and T2D onset at any age [OR = 1.19 (1.09-1.30), P = 1 × 10(-4) ]. The T2D risk allele also associated with lower acute insulin secretion (β = 0.88, as a multiplier, P = 0.02). Another intronic SNP (rs1334241, D' = 0.99, r(2) = 0.49 with rs2297627) associated with maximum adulthood BMI (β = 1.02, as a multiplier, P = 3 × 10(-5)), maximum childhood BMI z-score (β = 0.08, P = 3 × 10(-4)), and % body fat (β = 0.83%, P = 0.04).
Common variation in FOXO1A may modestly affect risk for T2D and obesity in American Indians.
之前在皮马印第安人中进行的一项全基因组关联研究（GWAS）发现，FOXO1A基因内的变异与早发型（发病年龄<25岁）2型糖尿病（T2D）存在适度关联。FOXO1A编码参与胰腺β细胞生长和下丘脑能量平衡的叉头转录因子；因此，在一个包含7710名美国印第安人的人群样本中，对FOXO1A作为T2D和肥胖症的候选基因进行了分析。
分析FOXO1A基因内/附近的标签单核苷酸多态性（SNP，次要等位基因频率≥0.05）与早发型T2D（n = 1060）、所有年龄段的T2D（n = 7710）以及胰岛素分泌（n = 298）之间的关联。还分析了这些SNP与成年期最大体重指数（BMI，n = 5918）、儿童期最大BMI z评分（n = 5350）以及体脂百分比（n = 555）之间的关联。
一个内含子SNP rs2297627与早发型T2D相关[比值比（OR）= 1.34（1.13 - 1.58），P = 8.7×10⁻⁴]，且与任何年龄的T2D发病相关[OR = 1.19（1.09 - 1.30），P = 1×10⁻⁴]。T2D风险等位基因还与较低的急性胰岛素分泌相关（β = 0.88，作为乘数，P = 0.02）。另一个内含子SNP（rs1334241，与rs2297627的D' = 0.99，r² = 0.49）与成年期最大BMI（β = 1.02，作为乘数，P = 3×10⁻⁵）、儿童期最大BMI z评分（β = 0.08，P = 3×10⁻⁴）以及体脂百分比（β = 0.83%）相关，P = .04。
FOXO1A基因的常见变异可能会适度影响美国印第安人患T2D和肥胖症的风险。
