| Objective The aim of this study is to explore the relationship between exposure to lead,cadmium,metallothionein gene polymorphism and neonatal birth defects,which in turn provides a scientific data for prevention of birth defects and the development of interventions.Method This study was based on the birth cohort of Guangxi Zhuang population.Women with 22-weeks,first-time pregnant were enrolled in the People's Hospital and Maternal and Child Health Hospital of Debao,Jingxi,Longan,Pingguo,Tiandong and other counties in Guangxi since June 2015.Participants' pregnancy outcomes were followed up,and their relevant biological specimens were collected.A nested case-control study was established on basis of the birth cohort,cases were pregnant women with birth defects and pregnant women with normal pregnancy outcomes were selected as the control group,matching on county and gestational age of cases.The concentration of lead,cadmium,and manganese in maternal plasma was determined by atomic absorption spectrophotometer(graphite furnace method).The single nucleotide polymorphism of metallothionein gene was detected by PCR-RFLP.Epidata3.0 was used for input of questionnaire data.Statistical analysis was conducted using SPSS22.0 software package.Chi-square test,Spearman correlation and multivariate logistic regression models were used to compare levels of lead,cadmium and manganese in pregnant women.Multivariate logistic regression was used to analyze the relationship between lead,cadmium,and manganese and birth defects in pregnant women,and the interaction of lead,cadmium and manganese exposure with metallothionein gene polymorphism on birth defects.The test level was a=0.05.Results 1.A total of 300 pregnant women(150 cases and 150 controls)of Zhuang nationality were included in the study.The age of the subjects was between 14 and 42 years,with an mean age of(28.8±5.5)years.The age of cases ranged from 14 to 42 years and the mean age was(29.2±5.9)years.The age of controls was from 17 to 41 years and the mean age was(28.37±5.09)years.After the balance test,the case group and the control group were There was no significant difference between cases and controls in the distribution of supplemented with folic acid in the age,occupation,parity,pregnancy,pre-pregnancy and pregnancy,the radiation exposure during the first half of pregnancy and pregnancy,pesticide exposure during the first half of pregnancy and pregnancy,factory near the house,cooking during pregnancy,cooking fuel,kitchen ventilation,fever during pregnancy,passive smoking during pregnancy,makeup during pregnancy,newly renovated house in the past five years,regular exercise(P<0.05).2.The median of blood lead level in pregnant women was 18.61?g/L(P25-P75:9.33?32.15?g/L).The median blood cadmium of pregnant women was 0.76?g/L(P25?P75:0.51?1.09?g/L).The median blood manganese level of pregnant women was 4.12?/L,and P25?P75 was 2.12?g/L?18.5?g/L.3.Spearman correlation analysis showed that blood lead level in pregnant women was positively correlated with cadmium level(correlation coefficient r=0.304,P<0.01),and lead level was negatively correlated with manganese level(correlation coefficient r=-0.131,P<0.05).Multivariate logistic regression analysis showed that among the factors affecting the heavy metal content in pregnant women,the ventilation of the kitchen was the influence factor for the blood lead concentration in pregnant women(P<0.01,OR=0.30,95%CI:0.16-0.55);Ventilation equipment is a influence factor for blood cadmium concentration in pregnant women(P<0.01,OR=0.41,95%CI:0.23-0.76).4.Chi-square test showed that there was a statistically significant difference in the frequency distribution of rs 10636 locus in MT-2A gene(P<0.05).The frequency distribution of alleles of rs 10636 locus in MT-2A gene was statistically significant(P<0.05).5.Mann-Whitney U test showed that the blood lead of the pregnant women in the case group and the control group was significant in the facial defects(P=0.019)and cardiovascular malformations(P=0.045).The blood cadmium of the pregnant women in the control group was only statistically significant in the subtypes of limb defects(P=0.021).For the blood manganese the case group and the control group only had the birth defects of phenylphenoneuria.There was no significant difference in the difference(P<0.05),but there was a statistical difference in blood cadmium content among pregnant women with other birth defects(P>0.05).7.Kruskal-Wallis H test results showed that the blood,lead,cadmium and manganese levels in pregnant women carrying MT-1A rs11076161 wild-type,heterozygous and mutant genes were not statistically significant(all P>0.05).There was no significant difference in the levels of lead,cadmium and manganese in the blood of pregnant women carrying wild-type,heterozygous and mutant genes in the MT-2A rs 10636 locus(all P>0.05).6.Univariate logistic regression analysis showed that elevated blood cadmium in pregnant women was a risk factor for birth defects(P<0.05,OR=1.88,95%CI:1.15-3.06),and elevated blood manganese was a risk factor for birth defects(P<0.01,OR=1.19,95%CI:1.09-1.30).Using age and occupation as adjustment factors,multivariate logistic regression analysis showed that pregnant women had elevated blood cadmium(P<0.05,OR=1.93,95%Cl:1.11-3.36)and elevated blood manganese(P<0.01,OR).=1.22,95%Cl:1.12-1.34),carrying the MT-2A rs10636 site mutation type genotype(P<0.05,OR=3.96,95%CI:1.02-15.39)was a risk factor for birth defects.7.Metal exposure-gene polymorphism interaction analysis:The exposure levels of lead,cadmium and manganese in pregnant women were combined with MT-1A rs11076161 and MT-2A rs10636,respectively.The results showed that there was an interaction between maternal manganese exposure and MT-2A rs10636 combination.Conclusion 1.Lead and cadmium may have homology to human exposure.2.High exposure to cadmium and manganese is a risk factor for birth defects;3.The rs10636 locus in MT-2A gene in mutant type may be a risk factor for birth defects,there was an interaction between maternal manganese exposure and MT-2A rs10636 combination. |
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