Yan-Hui He

Associations of CYP2A6 genotype with smoking behaviors in southern China

AIMS To investigate the association of CYP2A6 genetic polymorphisms with smoking-related phenotypes in Chinese smokers. DESIGN Case-only genetic association study. SETTING Southern China. PARTICIPANTS A total of 1328 Han Chinese smokers who participated in a community-based chronic disease screening project in Guangzhou and Zhuhai from 2006 to 2007. MEASUREMENTS All participants answered a structured questionnaire about socio-demographic status and smoking behaviors and informative alleles were genotyped for the cytochrome P450 2A6 (CYP2A6) gene (CYP2A6*4,*5,*7,*9 and *10). FINDINGS The frequencies of CYP2A6*4, *5, *7, *9 and *10 alleles were 8.5, 1.2, 6.3, 13.5 and 2.4%, which corresponded to 48.9, 15.4, 24.2 and 11.5% of participants being classified as normal, intermediate, slow and poor metabolizers, respectively. Multivariate analyses in male smokers demonstrated that compared with normal metabolizers, poor metabolizers reported smoking fewer cigarettes per day [adjusted odds ratio (OR) = 0.49; 95% confidence interval (CI): 0.32-0.76], started smoking regularly later in life (adjusted OR = 1.55; 95% CI: 1.06-2.26) and, among former smokers, reported smoking for a shorter duration prior to quitting (adjusted OR = 0.33; 95% CI: 0.12-0.94). However, poor metabolizers were less likely to quit smoking and remain abstinent than normal metabolizers (adjusted OR = 0.54; 95% CI: 0.34-0.86). CONCLUSIONS Reduced metabolism function of cytochrome P450 2A6 in smokers appears to be associated with fewer cigarettes smoked, later initiation of smoking regularly, shorter smoking duration and lower likelihood of smoking cessation.

The association between smoking quantity and hypertension mediated by inflammation in Chinese current smokers.

Objectives: Previous studies indicated that cigarette smokers were more likely to develop hypertension, and both smoking and hypertension were associated with inflammation. Whether inflammation mediates the relationship of them is unclear. This study aims to examine whether inflammation mediates the association between smoking and hypertension. Methods: Nine hundred and eighty-four Chinese current smokers from a community-based chronic diseases survey in Guangzhou and Zhuhai were interviewed about sociodemographics, smoking, chronic conditions, and other health-related variables. Hypertension was defined according to 2007 European Society of Hypertension and European Society of Cardiology (ESH-ESC) Practice Guidelines. Inflammatory markers including C-reactive protein (CRP), interleukin (IL)-6, IL-1&bgr;, monocyte chemoattractant protein-1 (MCP-1), tumor necrosis factor-&agr; (TNF-&agr;), and vascular cell adhesion molecule-1 (VCAM-1) were measured by flow cytometry. Logistic regressions were performed to assess the mediation of inflammation on the relationship between smoking quantity and hypertension. Results: We observed a positive association between smoking quantity and hypertension (P < 0.05). After controlling for potential confounders, daily cigarette consumption was significantly associated with higher level of CRP and VCAM-1 and lower level of TNF-&agr; among six measured inflammatory markers, and the current smokers with hypertension had significantly higher level of MCP-1 and CRP than those smokers who were normotensive. Furthermore, the association between smoking quantity and hypertension was mediated by CRP, which accounted for 58.59% of the estimated causal effect of smoking on hypertension. Conclusion: We have confirmed previous observations that smoking quantity was positively associated with hypertension, and the results of our study suggested that the association between smoking and hypertension was probably mediated by CRP.

Interaction between Maternal Passive Smoking during Pregnancy and CYP1A1 and GSTs Polymorphisms on Spontaneous Preterm Delivery

Objective The present study aimed to examine the association between maternal passive smoking during pregnancy and the risk of spontaneous PTD and to explore the potential interaction of the single or joint gene polymorphism of CYP1A1 and GSTs with maternal passive smoking on the risk of spontaneous PTD. Method We investigated whether the association between maternal passive smoking and PTD can be modified by 2 metabolic genes, i.e. cytochrome P4501A1 (CYP1A1) and glutathione S-transferases (GSTs), in a case-control study with 198 spontaneous preterm and 524 term deliveries in Shenzhen and Foshan, China. We used logistic regression to test gene-passive smoking interaction, adjusting for maternal socio-demographics and prepregnancy body mass index. Results Overall, maternal passive smoking during pregnancy was associated with higher risk of PTD (adjusted odds ratio = 2.20 [95% confidence interval: 1.56–3.12]). This association was modified by CYP1A1 and GSTs together, but not by any single genotype. For cross-categories of CYP1A1 Msp I and GSTs, maternal passive smoking was associated with higher risk of PTD among those women with CYP1A1 “TC/CC”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 2.66 [95% CI: 1.19–5.97]; P-value: 0.017). For cross-categories of CYP1A1 BsrD I and GSTs, maternal passive smoking was associated with higher risk of PTD only among those women with CYP1A1“AG/GG”+ GSTs “null”, but not among women with other genotypes; and this interaction was significant (OR = 3.00 [95% CI: 1.17–7.74]; P-value: 0.023). Conclusions Our findings suggest that the combined genotypes of CYP1A1 and GSTs can help to identify vulnerable pregnant women who are subject to high risk of spontaneous PTD due to passive smoking.

Comparison of secondhand smoke exposure measures during pregnancy in the development of a clinical prediction model for small-for-gestational-age among non-smoking Chinese pregnant women

Objective To compare predictive values of small-for-gestational-age (SGA) by different measures for secondhand smoke (SHS) exposure during pregnancy and to develop and validate a prediction model for SGA using SHS exposure along with sociodemographic and pregnancy factors. Methods We compared the predictability of different measures of SHS exposure during pregnancy for SGA among 545 Chinese pregnant women, and then used the optimal SHS measure along with other clinically available factors to develop and validate a prediction model for SGA. We fit logistic regression models to predict SGA by single measures of SHS exposure (self-report, serum cotinine and CYP2A6*4) and different combinations (self-report+cotinine, cotinine+CYP2A6*4, self-report+CYP2A6*4 and self-report+cotinine+CYP2A6*4). Results We found that self-reported SHS exposure alone predicted SGA (area under the receiver operating characteristic curve or area under the receiver operating curve (AUROC), 0.578) better than the other two single measures (cotinine, 0.547; CYP2A6*4, 0.529) or as accurately as combined SHS measures (0.545–0.584). The final prediction model that contained self-reported SHS exposure, prepregnancy body mass index, gestational weight gain velocity during the second and third trimesters, gestational diabetes, gestational hypertension and the third-trimester biparietal diameter Z-score could predict SGA fairly accurately (AUROC, 0.698). Conclusions Self-reported SHS exposure at peribirth performs better in predicting SGA than a single measure of serum cotinine at the same time, although repeated biochemical cotinine assessments throughout pregnancy may be optimal. Our simple prediction model is fairly accurate and can be potentially used in routine prenatal care.

Placenta mediates the association between maternal second-hand smoke exposure during pregnancy and small for gestational age

INTRODUCTION The causal relationship between maternal second-hand smoke (SHS) exposure during pregnancy and small for gestational-age (SGA) has been affirmed, but the mechanism is still unclear. Previous studies have found that the placenta remarkably affects fetal intrauterine growth and that SHS exposure during pregnancy impairs placental growth and decreases placental weight. Therefore, the placenta may mediate the association between maternal SHS exposure during pregnancy and SGA. This study explores whether and to what extent the association between maternal SHS exposure during pregnancy and SGA is mediated by the placenta. METHODS We investigated 562 pregnant women delivering SGA newborns (cases) and 1581 delivering appropriate-for-gestational-age newborns (controls) in this case-control study. Information on maternal SHS exposure during pregnancy, socio-demographic characteristics and obstetric conditions, including placental weight, were collected at the Maternity and Child Health Care Hospitals of Shenzhen and Foshan in Guangdong, China. Linear and hierarchical logistic regression models were fitted to examine the mediation effects of placental weight on the association between maternal SHS exposure during pregnancy and SGA. RESULTS After controlling for ethnicity, maternal age, educational level, family income, pre-pregnancy body mass index (BMI), parity, gestational age and newborn gender, maternal SHS exposure during pregnancy was associated with a higher SGA risk (adjusted odds ratio (OR) = 1.26; 95% confidence interval (CI) = 1.03-1.55) and lower placental weight (standard deviation (SD) = -0.15, SE = 0.04). Regression models illustrated that placental weight partially mediated (49.6%; 95% CI = 35.9-63.3%) the association between SHS exposure during pregnancy and SGA. DISCUSSION Our findings suggest that the placenta plays an intermediary role in how maternal prenatal SHS exposure affects fetal growth.

Influence of CYP2A6*4 Genotypes on Maternal Serum Cotinine Among Chinese Nonsmoking Pregnant Women

INTRODUCTION Serum cotinine is a common biomarker for smoking and secondhand smoke (SHS) exposure, but it can be affected by the activity of nicotine-metabolizing enzymes. This study investigated the influence of CYP2A6*4 genotypes on serum cotinine among nonsmoking pregnant women. METHODS We analyzed the data from 545 Chinese nonsmoking pregnant women in a case-control study on SHS exposure and birth outcomes in southern China. Participants self-reported their status and duration of SHS exposure during pregnancy right after delivery in hospital. Research staff used polymerase chain reaction to genotype CYP2A6*4 and enzyme-linked immunosorbent assay to measure cotinine levels in maternal serum samples collected before delivery. We stratified women by their self-reported SHS exposure status and CYP2A6*4 genotypes and then compared their median levels of serum cotinine. RESULTS Among women who self-reported non-SHS exposure (n = 317), the median serum cotinine levels were 2.83ng/ml for those with CYP2A6*1/*1 genotype, 1.39ng/ml for CYP2A6*1/*4, and 0.77ng/ml for CYP2A6*4/*4, respectively. Among women who self-reported SHS exposure (n = 228), the median cotinine levels were 3.32ng/ml for those with CYP2A6*1/*1 genotype, 2.38ng/ml for CYP2A6*1/*4, and 1.56ng/ml for CYP2A6*4/*4, respectively. Strikingly, self-reported SHS-exposed women with CYP2A6*1/*4 or CYP2A6*4/*4 genotype had significantly lower (rather than higher) median cotinine levels than self-reported non-SHS-exposed women with CYP2A6*1/*1 genotype (p = .012). CONCLUSIONS CYP2A6*4 genotype is associated with lower serum cotinine among Chinese nonsmoking pregnant women. Measuring CYP2A6*4 genotype may help to improve the validity of SHS exposure measurement by serum cotinine in pregnant women and possibly also in other nonpregnant populations.

Mediating role of maternal serum interleukin-1beta and tumor necrosis factor-alpha in the association between environmental tobacco smoke exposure in pregnancy and low birth weight at term

Abstract Objectives: To explore the mediation effects of maternal serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) on the association between environmental tobacco smoke (ETS) exposure during pregnancy and low birth weight (LBW) at term. Methods: ETS exposure, birth weight, blood sample and covariates were collected from 195 pregnant women delivered term LBW infants and 195 controls delivered normal birth weight infants in two Maternity and Child Hospitals in Guangdong, China. Maternal serum IL-1β and TNF-α were measured by flow cytometry. Logistic regression models and path analyses explored the mediation effects of maternal IL-1β and TNF-α on the association between ETS exposure and LBW. Results: LBW was significantly associated with maternal ETS exposure (OR = 2.14 (95% CI =1.06–4.32)). TNF-α and IL-1β were significantly associated with both LBW (OR = 1.87 (1.41–2.47) and OR = 1.53 (1.14–2.05)) and ETS (β = 0.32 (0.04–0.60) and β = 0.27 (0.05–0.49)). Traditional mediation analyses indicated the separate mediation effect of TNF-α and IL-1β was 32.2% and 24.6%, respectively. Path analysis revealed the combined mediation effects of TNF-α and IL-1β as 29.4% in the pathway from ETS exposure to LBW. Conclusions: Maternal serum IL-1β and TNF-α may play a mediating role in the association between maternal ETS exposure during pregnancy and term LBW.

The mediating role of placenta in the relationship between maternal exercise during pregnancy and full-term low birth weight

Abstract Objective: To explore the association of maternal exercise during pregnancy with full-term low birth weight (FT-LBW) and whether placenta mediates their association. Study design: We investigated 326 pregnant women delivering FT-LBW weight newborns (cases) and 1644 delivering full-term normal birth weight newborns (controls) in this case-control study. Information concerning maternal exercise during pregnancy, socio-demographics and obstetric characteristics were collected at Women and Children’s Hospitals of Shenzhen and Foshan in Guangdong, China. Results: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were significantly negatively associated with FT-LBW, respectively. Moreover, compared with mothers taking no exercise during pregnancy, those taking exercises were significantly negatively associated with FT-LBW except those taking low/medium frequency and short duration exercise and high-frequency and long duration exercise, and their adjusted ORs ranged from 0.30 to 0.62. Furthermore, mediation analysis illustrated that placental weight partially mediated 27.20% of the association between maternal exercise frequency during pregnancy and FT-LBW, but not the association between maternal exercise duration during pregnancy and FT-LBW. Conclusions: Maternal exercise during pregnancy is beneficial for lowering FT-LBW risk, especially when taking appropriate and enough exercise. Placenta weight partially mediates the association between maternal exercise frequency during pregnancy and FT-LBW.

A Simple Risk Score for Identifying Individuals with Impaired Fasting Glucose in the Southern Chinese Population

This study aimed to develop and validate a simple risk score for detecting individuals with impaired fasting glucose (IFG) among the Southern Chinese population. A sample of participants aged ≥20 years and without known diabetes from the 2006–2007 Guangzhou diabetes cross-sectional survey was used to develop separate risk scores for men and women. The participants completed a self-administered structured questionnaire and underwent simple clinical measurements. The risk scores were developed by multiple logistic regression analysis. External validation was performed based on three other studies: the 2007 Zhuhai rural population-based study, the 2008–2010 Guangzhou diabetes cross-sectional study and the 2007 Tibet population-based study. Performance of the scores was measured with the Hosmer-Lemeshow goodness-of-fit test and ROC c-statistic. Age, waist circumference, body mass index and family history of diabetes were included in the risk score for both men and women, with the additional factor of hypertension for men. The ROC c-statistic was 0.70 for both men and women in the derivation samples. Risk scores of ≥28 for men and ≥18 for women showed respective sensitivity, specificity, positive predictive value and negative predictive value of 56.6%, 71.7%, 13.0% and 96.0% for men and 68.7%, 60.2%, 11% and 96.0% for women in the derivation population. The scores performed comparably with the Zhuhai rural sample and the 2008–2010 Guangzhou urban samples but poorly in the Tibet sample. The performance of pre-existing USA, Shanghai, and Chengdu risk scores was poorer in our population than in their original study populations. The results suggest that the developed simple IFG risk scores can be generalized in Guangzhou city and nearby rural regions and may help primary health care workers to identify individuals with IFG in their practice.

Maternal exercise during pregnancy reduces the risk of preterm birth through the mediating role of placenta

Abstract Objective: The extent of research on maternal exercise during pregnancy and the risk of preterm birth (PTB) have grown substantially, but conclusions still remained controversial. Thus, this study aims to examine the relationship of maternal exercise during pregnancy and PTB and explore whether placenta mediates their relationship. Study design: We investigated 849 pregnant women delivering PTB newborns (cases) and 1306 delivering full-term appropriate for gestational age newborns (controls) in this case–control study. Information concerning maternal exercise during pregnancy, sociodemographics and obstetric characteristics were collected at Women and Children’s Hospitals of Shenzhen and Foshan in Guangdong, China. A series of logistic and linear regressions were used to examine the relationships of maternal exercise during pregnancy, placenta, and PTB. Results: After adjusting for the potential confounders, maternal exercise frequency and duration during pregnancy were negatively associated with PTB. Moreover, compared with mother taking no exercise during pregnancy, those taking exercise lowered the risk of PTB except those taking low/medium frequency and short duration exercise, and their adjusted ORs ranged from 0.43 to 0.65. Furthermore, mediation analysis illustrated that placental weight partially mediated 65.20% of the effects of maternal exercise frequency on PTB, as well as 41.98% of the association between maternal exercise duration and PTB. Conclusions: Maternal exercise during pregnancy is beneficial for lowering the risk of PTB, especially when taking appropriate and enough exercise. Placenta weight may partially mediate the association between maternal exercise during pregnancy and PTB.