Early puberty, higher obesity, and lower energy expendit

肥胖是美国的一个主要健康问题，与绝经后乳腺癌、子宫内膜癌和结肠癌以及糖尿病、高血压和冠心病的风险增加有关。根据国家健康与营养检查调查（NHANES）III，调整社会经济地位后，美国33%的成年人和22%的儿童超重，非裔美国女性的超重率是白人女性的两倍（1）。在过去的30年里，超重比例最显著的增长发生在非洲裔美国女孩中，她们经历了80 - 150%的年龄特异性增长，而白人女孩则增加了35%（2）。在类似的时间窗口内，非洲裔美国女孩初潮的平均年龄从12.5岁下降到12.0岁，而白人女孩则从12.8岁下降到12.5岁（3 - 4岁）。不仅是非洲裔美国女孩经历初潮的早期年龄，一个公认的乳腺癌的危险因素，但青春期开始的中位年龄发生在非洲裔美国女孩显着早于白人和墨西哥裔美国女孩在NHANES III。与西班牙裔和非西班牙裔白色同龄人相比，非洲裔美国育龄妇女雌二醇和孕酮的周期波动更大，排卵月经周期的百分比更高（Haimon C，2002），因此确定非洲裔美国妇女是美国其他种族群体中生命周期最长和内源性激素暴露循环水平最高的群体（6）。事实上，非洲裔美国妇女有可能在很长的生命周期内接触内源性激素，同时超重/肥胖的患病率也很高，这为这一族裔群体患主要成人癌症的高风险奠定了基础。遗传和生活方式因素的相互作用可能会影响从生命早期到青春期的线性生长速度，体重和成熟发育。细胞色素P 450 3A4 * 1B的一种高活性遗传变异体在睾酮代谢中占主导地位，在非洲裔美国人中的频率高于西班牙裔和非西班牙裔白人，并且在一项小型研究中与青春期开始时的年龄较早密切相关。因此，非洲裔美国女孩的特定子集可能具有赋予青春期提前风险增加的基因型，这是初潮提前的潜在风险因素。此外，最近的几份报告描述了高加索女孩的平均能量消耗高于非洲裔美国女孩，但结果与青春期状态不一致（12 - 14）。在拟议的研究中，我们试图调查环境，激素和遗传因素之间的关联影响种族群体的差异，在青春期阶段的非洲裔美国人和高加索女孩和试点测试的效用CYP3A4作为青春期提前的标志物。本研究设计为一项横断面研究（N = 400）健康，非糖尿病的非裔美国人和白人女孩的青春期前和青春期（年龄7 - 9.9岁）和他们的母亲。

Obesity is a major health problem in the United States associated with an increased risk of postmenopausal breast cancer, endometrial and colon cancers as well as diabetes, hypertension, and coronary heart disease. Based on the National Health and Nutrition Examination Survey (NHANES) III, 33% of adults and 22% of children in America are overweight, with a two-fold higher prevalence in African-American than Caucasian women, after adjustment for socioeconomic status (1). Over the past 30 years, the most dramatic increases in the proportion overweight has occurred in African-American girls, who have experienced age-specific increases of 80-150% compared to an increase of 35% in Caucasian girls (2). Over a similar window of time, the average age at onset of menarche in African-American girls has dropped from 12.5 to 12.0 years in contrast with a slower decline from 12.8 to 12.5 years in Caucasian girls (3-4). Not only are African-American girls experiencing an earlier age at menarche, a recognized risk factor for breast cancer, but the median age at onset of puberty occurs significantly earlier in African-American girls than in Caucasian and Mexican-American girls in NHANES III. African-American women of reproductive age have higher cyclic fluctuations of estradiol and progesterone and higher percentage of ovulatory menstrual cycles than their Hispanic and non-Hispanic white peers (Haimon C, 2002), thereby identifying African-American women as the group with the potential to have the longest life cycle and highest circulating levels of endogenous hormone exposures than other ethnic group in the United States (6). Indeed, African American women have the potential for a long life cycle of endogenous hormone exposures and a concomitantly high prevalence of overweight/obesity, which sets the stage for this ethnic group to be at high risk of the leading adult cancers. The interaction of genetic and lifestyle factors may influence the rate of linear growth, body mass, and maturational development from early life through adolescence. A high activity genetic variant of cytochrome P 450 3A4*1B, which predominates in testosterone catabolism, has a higher frequency in African-Americans than Hispanic and non-Hispanic whites and has been strongly associated with earlier age at onset of puberty in a small study. Thus a specific subset of African-American girls may have a genotype that confers increased risk of early puberty, a potential risk factor for early menarche. Moreover, several recent reports describe higher mean energy expenditure in Caucasian than African American girls, but findings are not consistent by pubertal status (12-14). In the proposed study, we seek to investigate the association between environmental, hormonal and genetic factors influencing ethnic-group differences in pubertal stage in African American and Caucasian girls and pilot test the utility of CYP3A4 as a marker of early puberty. This research is designed as a cross-sectional study of (N= 400) healthy, non-diabetic African-American and Caucasian girls of pre-pubertal and pubertal years (aged 7-9.9 y) and their mothers.