Roussel Ronan, Reis André F, Dubois-Laforgue Danièle, Bellanné-Chantelot Christine, Timsit José, Velho Gilberto
Service d'Immunologie Clinique, Hôpital Necker-Enfants Malades, Paris, France.
Clin Endocrinol (Oxf). 2003 Aug;59(2):237-41. doi: 10.1046/j.1365-2265.2003.01831.x.
A single nucleotide polymorphism (A1220G; N363S) in exon 2 of the glucocorticoid receptor gene (NR3C1), associated with increased sensitivity to glucocorticoids, was shown to be associated with obesity in nondiabetic subjects. Here, we investigated the impact of this variant on traits related to obesity and hyperglycaemia in subjects with type 2 diabetes mellitus.
The N363S variant was screened by restriction fragment length polymorphism technique following DNA amplification by polymerase chain reaction in 369 French Caucasians with type 2 diabetes mellitus.
Twenty subjects were found to be heterozygous for the variant (AG genotype frequency 0.0542). The prevalence of overweight [body mass index (BMI) > 25 kg/m2] was higher in AG carriers than in AA carriers (100%vs. 73%, P = 0.003). Moreover, the mean body weight and the BMI were higher in AG as compared to AA carriers, although only the body weight was significantly different between groups. However, when only the men were considered, a significantly higher BMI was observed in AG as compared to AA carriers: 30.0 +/- 4.8 vs. 27.3 +/- 4.6 kg/m2 (BMI Z-score 1.28 +/- 1.38 vs. 0.55 +/- 1.17; P = 0.035). No evidence was found for an association of the N363S variant with parameters related to the severity of hyperglycaemia.
The 363S allele of the N363S variant of NR3C1 is associated with the susceptibility to overweight in subjects with type 2 diabetes mellitus.
糖皮质激素受体基因（NR3C1）外显子2中的单核苷酸多态性（A1220G；N363S）与对糖皮质激素敏感性增加相关，已证实在非糖尿病受试者中与肥胖有关。在此，我们研究了该变异对2型糖尿病患者肥胖和高血糖相关性状的影响。
采用聚合酶链反应扩增DNA后，通过限制性片段长度多态性技术对369名法国2型糖尿病白种人进行N363S变异筛查。
发现20名受试者为该变异的杂合子（AG基因型频率为0.0542）。AG携带者中超重[体重指数（BMI）>25kg/m²]的患病率高于AA携带者（100%对73%，P = 0.003）。此外，AG携带者的平均体重和BMI高于AA携带者，尽管两组间仅体重有显著差异。然而，仅考虑男性时，AG携带者的BMI显著高于AA携带者：30.0±4.8对27.3±4.6kg/m²（BMI Z评分1.28±1.38对0.55±1.17；P = 0.035）。未发现N363S变异与高血糖严重程度相关参数之间存在关联的证据。
NR3C1基因N363S变异的363S等位基因与2型糖尿病患者超重易感性相关。
