Department of Pediatric Endocrinology, Erasmus Medical Center, Sophia Children's Hospital, Rotterdam, The Netherlands.
Horm Res Paediatr. 2011;76(5):307-13. doi: 10.1159/000330764. Epub 2011 Sep 14.
BACKGROUND/AIMS: Genetic variation in several candidate genes has been associated with short stature. Recently, a high-mobility group A2 (HMGA2) gene SNP has been robustly associated with height in the general population. Only few have attempted to study these genes in extremely tall stature. We therefore studied common genetic variation in candidate genes for height in extremely tall Dutch.
We included 116 constitutionally tall cases with height >2 SD and 103 controls with normally distributed height <2 SD. We genotyped 10 common polymorphisms previously associated with height variation.
The HMGA2 gene SNP was significantly associated with tall stature. Using a logistic regression model, we calculated that carrying the HMGA2 (rs1042725) C allele significantly increased the odds of being tall (OR = 1.53, 95% CI 1.02-2.28; p = 0.03). In addition, controls with one or two copies of the C allele were significantly taller than controls carrying the TT genotype [TC: mean (SD) +0.61 (0.21) SDS; p = 0.004, and CC: +0.77 (0.25) SDS; p = 0.003].
Our study shows that a common polymorphism in the HMGA2 gene is not only associated with height variation in the general population but also plays an important role in one of the extremes of the height distribution.
背景/目的：几个候选基因的遗传变异与身材矮小有关。最近，高迁移率族 A2（HMGA2）基因 SNP 与普通人群的身高有很强的相关性。只有少数人试图研究这些基因在极高身高中的作用。因此，我们研究了荷兰特高人群中候选基因的常见遗传变异。
我们纳入了 116 例身材高大的特发性身材矮小患者（身高>2 SD）和 103 例身高正常的对照者（身高<2 SD）。我们对 10 个先前与身高变化相关的常见多态性进行了基因分型。
HMGA2 基因 SNP 与身材高大显著相关。使用逻辑回归模型，我们计算出携带 HMGA2（rs1042725）C 等位基因显著增加了身材高大的几率（OR=1.53，95%CI 1.02-2.28；p=0.03）。此外，携带一个或两个 C 等位基因的对照组比携带 TT 基因型的对照组显著更高[TC：平均（SD）+0.61（0.21）SDS；p=0.004，和 CC：+0.77（0.25）SDS；p=0.003]。
我们的研究表明，HMGA2 基因的一个常见多态性不仅与普通人群的身高变化有关，而且在身高分布的一个极端中也起着重要作用。
