之间的关联研究微卫星标记在人类基因编码11 beta-hydroxysteroid脱氢酶1型和身体质量指数、腰围与臀围,糖皮质激素代谢。
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德雷伯N, Echwald SM拉威利GG,沃克EA,弗雷泽R,戴维斯E,索伦森TI, Astrup,亚当斯基J, Hewison M,康奈尔JM,皮德森O,斯图尔特点
之间的关联研究微卫星标记在人类基因编码11 beta-hydroxysteroid脱氢酶1型和身体质量指数、腰围与臀围,糖皮质激素代谢。
中国性金属底座。2002年11月,87 (11):4984 - 90。
- PubMed ID
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12414862 (在PubMed]
- 文摘
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两个同功酶11 beta-hydroxysteroid脱氢酶(11 beta-hsd)互换活动皮质醇(F)和非活动可的松(E)。11 beta-hsd1是oxo-reductase (E / F)表示在几个目标组织糖皮质激素,包括肝脏和脂肪组织,促进激素性糖质新生和脂肪细胞的分化,分别。我们已经分离出了一长篇HSD11B1基因克隆;基因是超过30 kb的长度,长度不9 kb之前报道,主要是由于大基因内区4。两个多态(CA) (n)重复特征已经在基因内区4:CA(19)重复2.7 kb 3的外显子4和CA(15)重复3 kb 5 '外显子5。微卫星,CA(19)和CA(15),使用荧光PCR扩增引物,并组ABI 377从413年的DNA DNA测序器正常个体参与的莫妮卡研究心血管疾病的风险因素和557年丹麦男人(ADIGEN研究),其中有234肥胖(体重指数(BMI)、> / = 31公斤/米(2)]在征兵委员会审查323年从被征召入伍者随机选择控制人口与BMI低于31公斤/米(2)(+ / - SE, 21.7 + / - 0.41)。从正常的基因型数据莫妮卡队列与性别、5 beta-tetrahydrocortisol + 5 alpha-tetrahydrocortisol /四氢可的松比率,腰臀部(W: H)的比例。当分析等位基因长度(0、1或2短等位基因)对CA(19)标记,有一个更高的趋势5 beta-tetrahydrocortisol + 5 alpha-tetrahydrocortisol /四氢可的松比率(P = 0.058)和W: H比(2和0.1短;P (c) = 0.10)短等位基因的传播。相反的是对CA(15)轨迹,与长等位基因在这个轨迹预测11 beta-hsd1活动增加,尤其是女性。从ADIGEN病例对照人群基因型数据与肥胖的临床标记如BMI和W: H比率。 There was no significant difference in the distribution of either microsatellite marker between lean and obese groups. Allele distributions were binomial, as seen for the MONICA cohort, and the data were split accordingly (zero, one, or two short alleles). No significant association was seen between grouped alleles and the clinical parameters. No association was observed between HSD11B1 genotype and BMI in either population. These data suggest that 11beta-HSD1 is not a major factor in explaining genetic susceptibility to obesity per se. However, weak associations between HSD11B1 genotype, increased 11beta-HSD1 activity, and W:H ratio suggest that polymorphic variability at the HSD11B1 locus may influence susceptibility to central obesity through enhanced 11beta-HSD1 activity (E to F conversion) in visceral adipose tissue.