Heude Barbara, Ong Ken K, Luben Robert, Wareham Nicholas J, Sandhu Manjinder S
Medical Research Council Epidemiology Unit, Strangeways Research Laboratory, Cambridge CB1 8RN, United Kingdom.
J Clin Endocrinol Metab. 2007 Jul;92(7):2734-8. doi: 10.1210/jc.2006-1948. Epub 2007 May 8.
The IGF2 gene (IGF2) plays a key role in growth and is a candidate for association with obesity. Previous studies have reported that polymorphisms in IGF2 are associated with body weight and body mass index (BMI), but the results have been inconsistent.
The aim of this study was primarily to confirm the association with BMI and, secondarily, to study the associations with other indices of body size.
In a sample of 2797 women and 2203 men aged 39-79 participating in the Norfolk arm of the European Prospective Investigation of Cancer, we genotyped three single nucleotide polymorphisms (SNPs) in the IGF2 gene that were previously associated with BMI [6815 A/T, 1156 T/C (G/A), and 820 G/A (ApaI)].
No significant associations were observed between these SNPs and BMI. However, all three SNPs were significantly associated with height (P = 0.03 to 0.001). In a backward elimination regression analysis, two SNPs, 1156 T/C (G/A) and 820 G/A, remained independently associated with height (P = 0.003 and P = 0.038, respectively). Haplotype analysis of these two SNPs showed that carriers of the GA haplotype were shorter than carriers of each of the other three haplotypes (P < 0.001 for all comparisons).
We did not confirm the previously reported associations between IGF2 polymorphisms and BMI. However, our results suggest that common variation in the IGF2 gene may be associated with adult height. IGF2 could be considered as a candidate gene for future research on mechanisms for the association between height and chronic diseases, such as cancer, diabetes, and coronary heart disease.
胰岛素样生长因子2基因(IGF2)在生长过程中起关键作用,是与肥胖相关联的一个候选基因。既往研究报道IGF2基因多态性与体重和体重指数(BMI)相关,但结果并不一致。
本研究的主要目的是确认与BMI的关联,其次是研究与其他身体尺寸指标的关联。
在参与欧洲癌症前瞻性调查诺福克队列研究的2797名39至79岁女性和2203名男性样本中,我们对IGF2基因中先前与BMI相关的三个单核苷酸多态性(SNP)进行了基因分型[6815 A/T、1156 T/C(G/A)和820 G/A(ApaI)]。
未观察到这些SNP与BMI之间存在显著关联。然而,所有三个SNP均与身高显著相关(P = 0.03至0.001)。在向后逐步回归分析中,两个SNP,即1156 T/C(G/A)和820 G/A,仍与身高独立相关(分别为P = 0.003和P = 0.038)。对这两个SNP的单倍型分析表明,GA单倍型携带者比其他三种单倍型的携带者更矮(所有比较的P < 0.001)。
我们未证实先前报道的IGF2基因多态性与BMI之间的关联。然而,我们的结果表明IGF2基因的常见变异可能与成人身高相关。IGF2可被视为未来研究身高与慢性疾病(如癌症、糖尿病和冠心病)关联机制的候选基因。