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，在调整社会经济地位后，非裔美国人的患病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裔美国女孩中，她们的年龄增长了80-150%，而白人女孩的年龄增长了35%(2)。在相似的时间段内，非裔美国女孩初潮的平均年龄从12.5岁下降到12.0岁，而白人女孩初潮的平均年龄从12.8岁下降到12.5岁（3-4）。在NHANES III中，非洲裔美国女孩不仅初潮年龄更早，这是乳腺癌的一个公认的危险因素，而且非洲裔美国女孩青春期开始的中位年龄明显早于白种人和墨西哥裔美国女孩。非裔美国育龄妇女的雌二醇和黄体酮的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），从而确定非裔美国妇女是美国其他种族群体中生命周期最长、内源性激素暴露循环水平最高的群体(6)。事实上，非洲裔美国妇女有潜在的长期内源性激素暴露的生命周期和随之而来的超重/肥胖的高发率，这为这个种族群体处于主要成人癌症的高风险中创造了条件。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、体重和成熟发育的速度。细胞色素p450 3A41B的高活性遗传变异在睾酮分解代谢中占主导地位，在非洲裔美国人中比西班牙裔和非西班牙裔白人的频率更高，并且在一项小型研究中与青春期开始的年龄较早密切相关。因此，非裔美国女孩的一个特定子集可能具有一种基因型，这种基因型会增加青春期提前的风险，这是月经初潮提前的潜在风险因素。此外，最近的几份报告描述了白人女孩比非裔美国女孩平均能量消耗更高，但研究结果与青春期状态不一致（12-14）。在本研究中，我们试图探讨环境、激素和遗传因素对非裔美国人和白种人女孩青春期阶段种族差异的影响，并对CYP3A4作为青春期早期标志的效用进行初步测试。本研究设计为一项横断面研究（N= 400）健康的非糖尿病美国黑人和高加索女孩青春期前和青春期（7-9.9岁）及其母亲。

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 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.