The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals.
The effect of FOXA2 rs1209523 on glucose-related phenotypes and risk of type 2 diabetes in Danish individuals.
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DOI：
10.1186/1471-2350-13-10
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发表时间：
2012-02-12
影响因子：
--
通讯作者：
Hansen T
中科院分区：
文献类型：
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作者：
Banasik K;Hollensted M;Andersson E;Sparsø T;Sandbaek A;Lauritzen T;Jørgensen T;Witte DR;Pedersen O;Hansen T
已经研究了FOXA家族内的变异对2型糖尿病（T2 D）风险的推定贡献，最近，在一项研究中，使用加权错误发现率控制程序来增强全基因组关联研究在检测低血糖之间关联方面的统计功效，据报道FOXA 2 rs 1209523的次要T等位基因与空腹血糖水平降低相关。频率变体和给定的性状。因此，本研究的主要目的是研究FOXA 2中rs 1205923的次要T等位基因是否与1）空腹血糖降低和2）发生T2 D的风险降低相关。其次，我们研究了FOXA 2中的rs 1205923是否与其他葡萄糖相关表型相关。使用KASPar® PCR SNP基因分型系统对来自四个不同研究人群的丹麦个体进行该变体的基因分型。我们研究了FOXA 2基因型与空腹血糖的相关性，并在基于人群的Inter 99研究中对6，162名丹麦人进行口服葡萄糖耐量试验后对胰岛素释放和胰岛素敏感性进行了估计，同时在10，196名丹麦人中评估了FOXA 2基因型与T2 D风险的相关性，包括四个不同的研究人群。在来自丹麦普通人群的葡萄糖耐受个体中，FOXA 2 rs 1209523与空腹血糖无关（效应量（β）= -0.03 mmol/l（95%CI：-0.07; 0.01），p = 0.2）。此外，当采用病例对照设置时，该变异在丹麦个体中显示与T2 D无关（比值比（OR）= 0.82（95%CI：0.62-1.07），p = 0.1）。然而，当我们在6，022名非肥胖个体（BMI < 30 kg/m2）的子集中进行分析时，观察到与T2 D的相关性（OR = 0.68（95%CI：0.49-0.94），p = 0.02）。此外，在非肥胖个体中，胰岛素释放和β细胞功能的几个指数与FOXA 2 rs 1209523的次要T等位基因相关。我们未能在基于葡萄糖耐受个体的人群样本中复制FOXA 2 rs 1209523的次要T等位基因与空腹血糖的相关性。为了充分阐明FOXA 2在葡萄糖稳态中的潜在作用，需要进行更广泛的研究。
Variations within the FOXA family have been studied for a putative contribution to the risk of type 2 diabetes (T2D), and recently the minor T-allele of FOXA2 rs1209523 was reported to associate with decreased fasting plasma glucose levels in a study using a weighted false discovery rate control procedure to enhance the statistical power of genome wide association studies in detecting associations between low-frequency variants and a given trait. Thus, the primary aim of this study was to investigate whether the minor T-allele of rs1205923 in FOXA2 associated with 1) decreased fasting plasma glucose and 2) a lower risk of developing T2D. Secondly, we investigated whether rs1205923 in FOXA2 associated with other glucose-related phenotypes. The variant was genotyped in Danish individuals from four different study populations using KASPar® PCR SNP genotyping system. We examined for associations of the FOXA2 genotype with fasting plasma glucose and estimates of insulin release and insulin sensitivity following an oral glucose tolerance test in 6,162 Danish individuals from the population-based Inter99 study while association with T2D risk was assessed in 10,196 Danish individuals including four different study populations. The FOXA2 rs1209523 was not associated with fasting plasma glucose (effect size (β) = -0.03 mmol/l (95%CI: -0.07; 0.01), p = 0.2) in glucose-tolerant individuals from the general Danish population. Furthermore, when employing a case-control setting the variant showed no association with T2D (odds ratio (OR) = 0.82 (95%CI: 0.62-1.07), p = 0.1) among Danish individuals. However, when we performed the analysis in a subset of 6,022 non-obese individuals (BMI < 30 kg/m2) an association with T2D was observed (OR = 0.68 (95%CI: 0.49-0.94), p = 0.02). Also, several indices of insulin release and β-cell function were associated with the minor T-allele of FOXA2 rs1209523 in non-obese individuals. We failed to replicate association of the minor T-allele of FOXA2 rs1209523 with fasting plasma glucose in a population based sample of glucose tolerant individuals. More extensive studies are needed in order to fully elucidate the potential role of FOXA2 in glucose homeostasis.