Early puberty, higher obesity, and lower energy expendit

在美国，肥胖是一个主要的健康问题，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。根据国家健康和营养检查调查(NHANES)III，美国33%的成年人和22%的儿童超重，经社会经济地位调整后，非洲裔美国人的超重率是高加索妇女的两倍。在过去的30年里，超重比例最显著的增长发生在非裔美国女孩中，他们经历了80%-150%的特定年龄增长，而白人女孩的增幅为35%(2)。在类似的时间窗口内，非裔美国女孩月经初潮开始的平均年龄从12.5岁下降到12.0岁，相比之下，高加索女孩的下降速度较慢，从12.8岁下降到12.5岁(3-4岁)。非裔美国女孩不仅月经初潮年龄较早，这是乳腺癌的公认危险因素，而且在NHANES III中，非裔美国女孩青春期开始年龄的中位数明显早于高加索和墨西哥裔女孩。育龄非洲裔妇女的雌二醇和孕酮周期波动比西班牙裔和非西班牙裔白人同龄人更高，排卵月经周期的百分比也更高(Haimon C，2002)，从而确定非洲裔妇女比美国其他族裔群体有可能具有最长的生命周期和最高的内源性激素循环水平(6)。事实上，非洲裔美国女性有可能在很长的生命周期内暴露于内源性激素，并伴随着超重/肥胖的高流行率，这为这一种族群体处于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早年到青春期的线性生长、体重和成熟发育的速度。在一项小型研究中，细胞色素P450 3A41B的一种高活性基因变体在非裔美国人中的出现频率高于西班牙裔和非西班牙裔白人，并与青春期开始时的较早年龄密切相关。因此，非洲裔美国女孩中的一个特定亚群可能具有一种基因，这种基因可能会增加青春期提前的风险，这是导致月经初潮提前的一个潜在风险因素。此外，最近的几份报告描述了高加索女孩比非裔美国女孩更高的平均能量消耗，但青春期状况的研究结果并不一致(12-14岁)。在这项拟议的研究中，我们试图调查环境、激素和遗传因素对非裔美国人和高加索女孩青春期阶段种族差异的影响，并初步测试CYP3A4作为青春期早期标志的实用性。本研究旨在对(N=400)处于青春期前和青春期(7-9.9岁)的健康、非糖尿病的非裔美国人和高加索人女孩及其母亲进行横断面研究。

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 3A41B, 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.