Puberty In Chinese Girls Research Articles

Association of obesity and menarche SNPs and interaction with environmental factors on precocious puberty.

Obesity is an important cause for the precocious or early puberty. However, the association between obesity-related loci and the risk of precocious puberty as well as the effect of gene-environment interaction are unclear, especially in the Chinese children population. This was a case-control study using baseline data from two cohorts and hospital cases in China. 15 SNPs loci and several environmental factors were included in the analysis of 1201 participants. Chi-square test and logistic regression were used to analyze the association between SNPs and precocious puberty. Additionally, exploratory factor analysis was conducted on 13 environmental variables, and then to explore their interaction with genes on precocious puberty. The effect allele C of rs571312, and G of rs12970134MC4R were associated with precocious puberty in girls with obesity. Regarding the gene-environment interaction, we found that when girls were in the high socioeconomic status, the rs571312 (OR: 3.996; 95% CI: 1.694-9.423) and rs12970134 (OR: 3.529; 95% CI: 1.452-8.573) risk genotypes had a greater effect on precocious puberty. The obesity risk gene polymorphisms MC4R rs571312 and rs12970134 were associated with precocious puberty in Chinese girls with obesity, and girls with risk genotypes and high socioeconomic status should be given extra attention. This is the first study that identified the association between rs571312 and rs12970134 of MC4R gene and precocious puberty in Chinese children. We found that when girls were in the high socioeconomic status, the risk genotypes of rs571312 and rs12970134 had a greater effect on precocious puberty. The results of this study have great public health implications. It is recommended that girls who are in high socioeconomic status and have a high genetic risk for early sexual maturity should closely monitor their pubertal development and consider early intervention strategies.

Dietary pattern and precocious puberty risk in Chinese girls: a case-control study

BackgroundThe role of dietary intake on precocious puberty remains unclear. This study aimed to investigate the association between the amount and frequency of dietary intake and the risk of precocious puberty in Chinese girls.MethodsIn this case-control study, we enrolled 185 precocious puberty girls and 185 age-matched controls. Their dietary intake was assessed through a semi-quantitative food frequency questionnaire. Their sociodemographic and lifestyle data were collected. The associations between dietary intake and risk of precocious puberty were assessed by conditional logistic regression models.ResultsAfter multivariate adjustment, consuming a higher amount of red meat was associated with higher precocious puberty risk (OR = 2.74, 95% CI: 1.25–6.02), while a higher frequency of fruit ( P for trend = 0.024) and amount of vegetable intake was associated with a lower risk of precocious puberty (P for trend = 0.002). The high vegetable and protein dietary pattern was significantly negatively associated with precocious puberty (OR = 0.78, 95% CI: 0.63–0.97), whereas the high animal food and fruits dietary pattern was remarkably positively associated with precocious puberty (OR = 1.36, 95% CI: 1.09–1.69), after adjusting for age and body mass index.ConclusionsHigh vegetable and protein dietary pattern is a protective factor against precocious puberty, while high animal food and fruits dietary pattern is a risk factor for precocious puberty in Chinese girls. Attentions should be paid to a reasonable intake of red meat, eggs, and fruits in children’s daily diet, increase their intake of vegetables, in order to reduce the risk of precocious puberty.

Association of the KISS1, LIN28B, VDR and ERα gene polymorphisms with early and fast puberty in Chinese girls

Objectives To explore the association of KISS1, LIN28B, vitamin D receptor (VDR), and estrogen receptor α (ERα) gene polymorphisms and the risk of early with fast puberty (EFP) risk, and with hormone levels in EFP cases, in Chinese girls. Methods The analysis was based on the data of 141 girls with EFP and 152 girls without EFP. Clinical features were documented, and all SNP genotyping was conducted using SNaPshot method. Statistical analysis was performed to assess the association of the SNPs with EFP risk, and with hormone levels in EFP cases. Results There was a significant association between rs7759938-C polymorphism in the LIN28B gene and the risk for EFP in the recessive (TT + CT vs. CC) model (p = 0.040). Remarkably, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene were significantly associated with peak LH (luteinizing hormone) levels (p = 0.008, 0.045) and peak LH/FSH (follicle-stimulating hormone) ratio (p = 0.007, 0.006). Additionally, on 7 of the 8 variant loci the alleles associated with increased levels of both peak LH levels and peak LH/FSH ratio in EFP cases were also associated with increased CPP risk. Conclusions Our findings indicate that rs7759938-C polymorphism in the LIN28B gene might have a protective effect on EFP susceptibility. The most striking findings of this study is that, rs5780218-delA polymorphism in the KISS1 gene and rs2234693-C polymorphism in the ERα gene influenced levels of GnRH-stimulated peak LH and LH/FSH ratio, and in general CPP risk genes might also contributes to the abnormality of hormonal levels in EFP.

Efficacy of Leuprorelin 3-Month Depot (11.25 mg) Compared to 1-Month Depot (3.75 mg) for Central Precocious Puberty in Chinese Girls: A Prospective Cohort Study.

A 3-month depot of leuprorelin acetate (LA) was introduced in China in July 2020. However, the clinical experience is limited. The purpose of this study was to compare the efficacy of a LA 11.25 mg 3-month depot with that of a 3.75 mg 1-month depot in suppressing pubertal development for the treatment of central precocious puberty (CPP). Subjects and Methods. A prospective study, including 78 girls with CPP treated with LA, was conducted. 31 patients were treated with a LA 3-month depot, and 47 were treated with a LA 1-month depot. Participants were interviewed at baseline and 6 months. Anthropometric, metabolic, and reproductive data were assessed at each interview. Bone age, serum endocrine hormones, maximum diameter of uterus and volume of ovary of each patient were evaluated. A pharmacoeconomic evaluation was also conducted. Treatment with a 3-month depot was similar to treatment with a 1-month depot in terms of baseline characteristics. After 6 months of treatment, a suppressed level of luteinizing hormone (LH) (LH < 2.5 IU/L) was found in 100% and 95% of the 11.25 mg and 3.75 mg groups, respectively. LH decreased from 2.11 ± 1.83 and 2.82 ± 2.31 at baseline (P=0.172) to 0.37 ± 0.39 and 0.44 ± 0.76 (P=0.758) in the 3-month and 1-month groups, respectively. Follicle stimulating hormone and estradiol levels, bone age/chronological age (BA/CA), height velocity, maximum diameter of uterus and volume of ovary did not show any distinction between the two groups after 6 months of treatment, but both were significantly ameliorated compared with the baseline. The loss of working time of parents and study time of patients and the numbers of visits, injections and laboratory examinations obviously decreased in the 3-month depots. An LA 3-month depot was equally effective and safe as a 1-month depot for hormonal suppression and bone maturation inhibition, providing clinical experience in China. The 11.25 mg depot of LA is a safe, efficient, and economical treatment method for the advanced activation of the hypothalamic-pituitary-gonadal (HPG) axis.

The use of morning urinary gonadotropins and sex hormones in the management of early puberty in chinese girls

The use of morning urinary gonadotropins and sex hormones in the management of early puberty in chinese girls

Obesity-related genetic polymorphisms are associated with the risk of early puberty in Han Chinese girls.

To explore the association between obesity and precocious puberty from the perspective of genetic polymorphism. Two hundred and ninety-eight pairs of girls in early puberty and age-matched controls (±3 months) were recruited. The genotypes of four obesity-related single-nucleotide polymorphism (SNP) loci (rs10968576, rs12935153, rs4674340 and rs7635103) were determined and the effect of variation on early puberty in Chinese Han girls was evaluated. The unstimulated luteinizing hormone (LH), follicle-stimulating hormone and estradiol levels were also measured to determine the relationship with SNP polymorphisms. The effect allele A of rs12935153 was associated with early puberty (odds ratio [OR] = 1.256, 95% confidence interval [CI]: 1.010-1.585), but the significance disappeared after multiple comparisons. After adjusting for body mass index, rs12935153 variation increased the risk of early puberty in additive (OR = 1.589, 95% CI: 1.222-2.066), dominant (OR = 1.788, 95% CI: 1.210-2.642) and recessive (OR = 1.915, 95% CI: 1.207-3.038) models of inheritance. Individuals harbouring AA genotype in rs12935153 had a risk of higher LH levels than that of wild type (OR = 1.668, 95% CI: 1.093-2.546). The association between obesity and precocity can be explained from a genetic perspective. Our study suggests that variations in rs12935153 increase the risk of early puberty in Chinese girls. Further studies are needed to verify our findings.

The Use of Morning Urinary Gonadotropins and Sex Hormones in the Management of Early Puberty in Chinese Girls.

ContextAlthough gonadotropin-releasing hormone stimulation test (GnRHST) is the gold standard in diagnosing central precocious puberty (CPP), it is invasive, expensive, and time-consuming, requiring multiple blood samples to measure gonadotropin levels.ObjectiveWe evaluated whether urinary hormones could be potential biomarkers for prepuberty or postpuberty, aiming to simplify the current diagnosis and prognosis procedure.MethodsWe performed a cross-sectional study of a total of 355 girls with CPP in National Clinical Research Center for Child Health in China, including 258 girls with positive and 97 girls with negative results from GnRHST. Twenty patients received GnRH analogue (GnRHa) treatment and completed a 6-month follow up. We measured luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol, prolactin, progesterone, testosterone, and human chorionic gonadotropin in the first morning voided urine samples.ResultsTheir urinary LH levels and the ratios of LH to FSH increased significantly with the advancement in Tanner stages. uLH levels were positively associated with basal and peak LH levels in the serum after GnRH stimulation. A cutoff value of 1.74 IU/L for uLH reached a sensitivity of 69.4% and a specificity of 75.3% in predicting a positive GnRHST result. For the combined threshold (uLH ≥ 1.74 + uLH-to-uFSH ratio > 0.4), the specificity reached 86.6%. After 3 months of GnRHa therapy, the uLH and uFSH levels decreased accordingly.ConclusionuLH could be a reliable biomarker for initial CPP diagnosis and screening; uLH could also be an effective marker for evaluating the efficacy of clinical treatment.

Association of Polymorphisms in the Kisspeptin/GPR54 Pathway Genes With Risk of Early Puberty in Chinese Girls.

This case control study was designed to investigate the association between mutation of 10 single nucleotide polymorphism (SNP) loci (rs1132506, rs5780218, rs192636495, rs4889, rs184749, rs12985070, rs708910, rs932491, rs8074995, and rs2306877) in all 5 genes (KISS1, GPR54, PLCB1, PRKCA, and ITPR1) in the kisspeptin/GPR54 pathway and the risk of early puberty in Chinese Han girls. A total of 314 pairs of early puberty girls on their first visit to hospital and age-matched controls (± 3 months) were recruited. The genotypes of each SNP were determined and the effect of loci variation on early puberty was investigated. rs5780218 was significantly associated with early puberty in additive, dominant, and recessive models of inheritance after adjusting for confounding factors (Pr < .05). After stratification, rs5780218 variation (odds ratio [OR], 1.650, 95% confidence interval [CI], 1.155-2.355 in additive models and OR, 2.116; 95% CI, 1.187-3.770 in recessive models) increased the risk of central precocious puberty (CPP); mutation in rs708910 (OR, 2.768; 95% CI, 1.305-5.872 in recessive model) had a positive association with the risk of CPP; and rs932491 variation was negatively associated with early and fast puberty (EFP) (OR, 0.309; 95% CI, 0.144-0.661 in additive models and OR, 0.317; 95% CI, 0.141-0.713 in dominant models). Our study suggests that mutation in rs5780218 and rs708910 increases the risk of CPP. rs932491 variation may have a protective effect on the risk of EFP. Further studies in larger populations or with people from different regions are needed to verify our findings.

Long-Term Outcomes of Treatments for Central Precocious Puberty or Early and Fast Puberty in Chinese Girls.

Gonadotropin-releasing hormone analogues (GnRHa) and recombinant human growth hormone (rhGH) have been widely used to treat idiopathic central precocious puberty (CPP) or early and fast puberty (EFP). However, large-scale studies to evaluate the treatment effects on final adult height (FAH) are still lacking. To assess the effects of long-term treatment for CPP/EFP on FAH and its main influencing factors. Retrospective, multicenter observational study from 1998 to 2017. Four hundred forty-eight Chinese girls with CPP/EFP received GnRHa and rhGH treatment (n = 118), GnRHa alone (n = 276), or no treatment (n = 54). FAH, target height (Tht), and predictive adult height (PAH). The height gain (FAH-PAH) was significantly different among the GnRHa and rhGH treatment, GnRHa alone, and no treatment groups (P < 0.05; 9.51 ± 0.53, 8.07 ± 0.37, and 6.44 ± 0.91 cm, respectively). The genetic height gain (FAH-Tht) was 4.0 ± 0.5 cm for the GnRHa + rhGH group and 2.0 ± 0.27 cm for the GnRHa group, while the control group reached their Tht. In addition, 5 critical parameters derived from PAH, bone age, and Tht, showed excellent performance in predicting which patients could gain ≥5 cm (FAH-PAH), and this was further validated using an independent study. The overall beneficial effect of GnRHa + rhGH or GnRHa on FAH was significant. The control group also reached their genetic target height. Clinicians are recommended to consider both the potential gains in height and the cost of medication.

Observational study pelvic ultrasound a useful tool in the diagnosis and differentiation of precocious puberty in Chinese girls.

Rapid and noninvasive diagnosis on and differentiation between normal, central precocious puberty (CPP), and isolated precocious puberty (IPP) is imperative before a decision can be made with gonadotropin-releasing hormone (GnRH) agonist treatment. Our study aims to evaluate such a role by pelvic ultrasound.We consecutively enrolled 84 cases of IPP (59 with premature thelarche/ pubarche and 25 with premature menarche), 47 CPP, and 177 age-matched normal controls. The IPP and CPP were diagnosed by clinical examination and GnRH-stimulation test and confirmed by over 2 years’ follow-up. All subjects underwent pelvic ultrasound examination for length, width, thickness, volume of uterine/cervix/ovaries, fundal/cervical thickness ratio, endometrial thickness, and averaged maximal diameter of largest follicles. Statistical comparisons of these sonographic parameters between disease groups were made according to age intervals.It was found that between CPP and normal girls, 10 and 12 ultrasound parameters differed significantly in the >6 to 8 and >8 to 10 years age interval, respectively. Cervical thickness and endometrial thickness was the best discriminating parameter in the 2 intervals by receiver operating characteristic (ROC) curve analysis, and the cutoff, sensitivity and specificity associated with was 0.73 cm, 93.30%, 85.70%, and 0.26 cm, 76.92%, 100%, respectively. Between CPP and IPP, 2 and 5 parameters differed significantly in the >6 to 8 and >8 to 10 years age interval. Cervical length was the best discriminating parameter in both age intervals. The cutoff, sensitivity, and specificity associated were 1.49 cm, 93.33%, 55.17%, and 1.88 cm, 100%, 71.43%, respectively; Finally between normal and IPP girls, 4, 7, and 5 parameters differed significantly in the 0 to 6, >6 to 8, and >8 to 10 years intervals, respectively. Ovarian thickness, ovarian width, and cervix thickness was the best parameter for the 3 age interval respectively, and the cutoff, sensitivity and specificity associated were 0.98 cm, 76.46%, 84.85%, 1.39 cm, 85.71%,73.81%, and 0.75 cm, 90.48%, 64.21%, respectively.Our results indicate that pelvic ultrasonography could serve as a complementary tool for differentiation between normal girls and girls with different forms of sexual precocity in China. The best discriminating parameter changes according to precocity forms and age intervals.

Association of pyrethroids exposure with onset of puberty in Chinese girls

Pyrethroids, a class of ubiquitous insecticides, have been considered as endocrine-disrupting chemicals (EDCs). Female animal studies suggested that early-life pyrethroids exposure might delay puberty onset. However, it remains unclear whether this association applies to human populations. A total of 305 girls at the ages of 9–15 years old were recruited in Hangzhou, China in this study. The concentration of the common metabolite of pyrethroids, 3-phenoxybenzoic acid (3-PBA), was analyzed in urine samples to reflect the exposure level of pyrethroids. The associations of 3-PBA with pubertal stages were evaluated using a multinomial logistic regression model. The geometric mean level of 3-PBA was 1.11 μg/L (1.42 μg/g for creatinine-adjusted concentration). There was a significant 45% reduction in odds of being in breast stage 3 (B3) per one-unit increase in the log-transformed 3-PBA levels [OR = 0.55 (95%CI: 0.31–0.98), p = 0.042]. A similar negative association was found between urinary 3-PBA levels with later onset by pubic hair stage 2 (P2) [OR = 0.56 (95%CI: 0.36–0.90), p = 0.015]. Similar negative association was also observed between urinary 3-PBA levels and pubertal onset indicated by menarche [OR = 0.51 (95%CI: 0.28–0.93), p = 0.029]. For the first time to our knowledge, this work reveals that pyrethroids exposure may increase the risk of delayed pubertal onset in girls.

Effects of pomegranate extract in supplementing gonadotropin-releasing hormone therapy on idiopathic central precocious puberty in Chinese girls: a randomized, placebo-controlled, double-blind clinical trial.

Central precocious puberty (CPP) without organic abnormality is called idiopathic CPP (ICPP). The objective of this trial was to evaluate the effects of pomegranate extract in supplementing gonadotropin-releasing hormone (GnRH) analog therapy on ICPP-affected girls in the Chinese population. 286 girls, diagnosed with ICPP were initially enrolled into this trial, and among them 225 eligible patients were randomized to receive a combinational GnRH analog treatment supplemented with either a placebo or pomegranate extract on a daily basis for a period of 3 months. Their demographics, secondary sexual characteristics and hormone profiles were analyzed at baseline and end of trial. After 3 months of treatment, demographic profiles including bone age, growth velocity and height standard deviation score for bone age, and secondary sexual characteristics including uterus and ovary volume, as well as serum hormone profiles including estradiol, peak luteinizing hormone and insulin-like growth factor 1 were all significantly improved in girls receiving a combinational treatment of both GnRH analog and pomegranate extract. Daily consumption of pomegranate extract was able to supplement and improve the treatment outcomes of the GnRH analog therapy for ICPP in Chinese girls.

Association study of TAC3 and TACR3 gene polymorphisms with idiopathic precocious puberty in Chinese girls.

The allele variant of neurokinin B and its receptor genes were thought important in regulating the human reproductive axis in many populations. The aim of this study was to investigate whether the variances in TAC3 and TACR3 genes that encoded neurokinin B (NKB) and its receptor (NK3R), individually, were associated with idiopathic precocious puberty in Chinese girls. The genotyping method of polymerase chain reaction-restriction fragment length polymorphism was applied in this study; the distribution of five active single nucleon acid polymorphisms (SNPs) in TAC3 (p.G34R, p. A63P, p.Q66*, p.S99P, and a mutation on 5' UTR) and four sites in TACR3 (A29V or G, G59E, S455G, and A449S or T) genes was analyzed in 267 healthy and 186 idiopathic precocious puberty Chinese girls. Among the nine active SNPs, only A63P in TAC3 gene showed statistical differences; the p value was 0.024. A63P in TAC3 gene was statistically associated with the puberty onset time in Chinese girls.

An association study between the genetic polymorphisms within GnRHI, LHβ and FSHβ genes and central precocious puberty in Chinese girls

Objectives: Gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are three hypothalamic–pituitary–gonadal axis expressing hormones. They play critical roles in the onset of puberty. Here we report the relationship between the three hormones and Central Precocious Puberty (CPP) in Chinese Han girls. Methods: We analyzed the single nucleotide polymorphisms (SNPs) of 5′-flanking regions of these genes by DNA sequencing in 27 CPP samples. Then the SNPs sites were genotyped by ligase detection reaction in a total of 283 Chinese Han CPP cases and 284 matched controls. Distributions of the polymorphisms and haplotypes were calculated for statistical evaluation. Results: Nine SNPs (One in GnRHI gene: −2003 C/T; Five in LHβ gene: −1456 C/G, −1424 C/G, −238 G/A, −164 G/A and −34 T/A; Three in FSHβ gene: −1825 T/C, −261 G/T and −132 T/A.) were found. A quantitative genetic association study was made. −1825 T/C in FSHβ gene was related with CPP with a weak effect ( P = 0.025). A haplotype in the 5′-flanking region of LHβ gene was significantly associated with CPP in Chinese Han girls ( P = 8.25 × 10 −09). However, analysis software showed that none of SNP was found in the regulating control element of these genes. Conclusions: Our finding implies that the polymorphisms in the 5′-flanking regions of FSHβ gene and LHβ gene probably were related to the puberty onset time of these girls. Further studies on the polymorphisms are needed for the exact mechanism.

Growth and Bone Mineral Accretion During Puberty in Chinese Girls: A Five-Year Longitudinal Study

There are few longitudinal data on bone development during puberty in children with low calcium intake. This 5-yr longitudinal study showed that, in Chinese girls, the mean apparent calcium retention efficiency during puberty was 40.9%, PHV occurred at 3-0 yr before menarche, and peak bone mineral accretion occurred 1 yr later than PHV. Chinese girls have high calcium retention efficiency during puberty. There are few longitudinal data on bone development during puberty in children with low dietary calcium intake. The aim of this study was to examine the rate of growth and bone mineral accretion and study the predictors of total body BMC during puberty in a 5-yr longitudinal study with Chinese girls. Ninety-two girls, 9.5-10.5 yr of age at baseline, from the unsupplemented control group of a school milk intervention trial were included in this analysis. Data on anthropometric measurements, total body BMC as assessed by DXA, and calcium intake as assessed by a 3-day food record were obtained at baseline and 1, 2, 4, and 5 yr. The mean age of menarche was 12.1 +/- 1.0 yr. The mean annual rate of bone mineral accretion was 197.4 g/yr during the follow-up period, representing a calcium accretion rate of 162.3 mg/d. This calcium retention rate and the average dietary calcium intake of 444.1 mg/d gave an apparent calcium retention efficiency of 40.9%. Peak height velocity (PHV) occurred at 3-0 yr before menarche. Peak bone mineral accretion occurred 1 yr later than PHV. There was a decrease in size-corrected BMD in the year before menarche. In the linear mixed-effects model analysis containing body size and lifestyle factors, we found that height, body weight, and calcium intake were significant independent predictors of total body BMC. Chinese girls with low habitual dietary calcium intake have high calcium retention efficiency during puberty. Because calcium intake is a significant predictor of total body BMC, increasing dietary calcium intake may have beneficial effects on bone mineral accretion in these girls.

Association study of the polymorphisms in the KISS1 gene with central precocious puberty in Chinese girls

The kisspeptin/GPR54 pathway has been proven to be crucial in the process of puberty onset, yet the polymorphisms in the KISS1 gene and their relationships with central precocious puberty (CPP) have not been investigated. This study was performed to reveal the relationship between the gene and the disease. 272 Chinese Han girls diagnosed to be CPP patients were recruited as Case Group I, 43 unrelated African women as Case Group II, and 288 unrelated normal Chinese Han girls as Control Group. Polymorphism scans of the KISS1 gene were performed for the first time by bidirectional resequencing of the whole gene in a subset of the patients, and then by ligase detection reaction some of the polymorphisms identified were typed in the two groups and the respective haplotypes were constructed. The relationships of the typed polymorphisms and the haplotypes with CPP were evaluated by an association study between genotypes and phenotypes. By resequencing, eight polymorphisms were identified, five of which were typed forming 18 haplotypes. Although one novel nonsynonymous single nucleotide polymorphism substituting one amino acid in kisspeptin (P110T) was found to be statistically related to the disease (P = 0.025), no further supporting evidence has yet been found. The other polymorphisms and all the haplotypes were not found to be related. The polymorphism scanning and typing of KISS1 uncovered several potentially meaningful polymorphisms, but the conclusion was not solid and further studies are necessary for function validation of these polymorphisms.

Association study of four activity SNPs of CYP3A4 with the precocious puberty in Chinese girls

CYP3A4 plays an important role in the metabolism of a variety of endogenous and exogenous compounds. Earlier studies revealed that a high-activity variation of the CYP3A4 gene, CYP3A4*1B is significantly associated with the precocious puberty in girls. Other three variations, CYP3A4*4, CYP3A4*5 and CYP3A4*6, which were found in a study carried out in a Chinese population in Taiwan, were reported to down-regulate the enzymatic activity of CYP3A4. The four activity SNPs were typed in our study in two groups of Chinese girls: 176 girls with precocious puberty as the case group, and 192 normal girls as the control group. No variations of CYP3A4*1B and CYP3A4*4 were found in all the cases and controls. Heterozygous of CYP3A4*5 was found in five subjects of the 192 controls but none in the cases, heterozygous of CYP3A4*6 was found in two subjects of the controls but none in the cases. Fisher's exact test showed that the variation of CYP3A4*5 was associated with the onset of puberty in Chinese girls ( P-trend = 0.038), while the variation of CYP3A4*6 was not associated with the onset of puberty in Chinese girls ( P-trend = 0.272). The result suggests that these mutations in the CYP3A4 gene have no contribution to the early onset of puberty in Chinese girls, but are related in some way with the puberty development in Chinese girls.