评估FOXO1A作为美国印第安人2型糖尿病和肥胖潜在易感基因座的情况。
Assessing FOXO1A as a potential susceptibility locus for type 2 diabetes and obesity in American Indians.
作者信息
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
机构信息
Phoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes Of Health, Phoenix, Arizona, USA.
出版信息
Obesity (Silver Spring). 2015 Oct;23(10):1960-5. doi: 10.1002/oby.21236. Epub 2015 Sep 4.
OBJECTIVE
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.
METHODS
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).
RESULTS
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).
CONCLUSIONS
Common variation in FOXO1A may modestly affect risk for T2D and obesity in American Indians.
目的
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。
方法
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。
结果
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。
结论
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。
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