Correlation between maternal vitamin D receptor gene FokI locus polymorphism and congenital hypothyroidism susceptibility
Objective To explore the correlation between maternal vitamin D receptor gene(VDR)FokI locus polymorphism and congenital hypothyroidism(CH)susceptibility.Methods From January 2020 to December 2022,a total of 140 mothers of CH newborns were enrolled as study group,which aged 22-37 years old with mean age of 30.94 years old;gestational age of 35-41 weeks with mean of 39.02 weeks;126 cases of natural conception;pre-pregnancy body mass was 46.0-76.2 kg with mean body mass of 55.62 kg;number of births was 1-3 times with mean of 1.62 times;94 cases of sponta-neous delivery and 46 of cesarean section;43 cases living in urban and 97 in rural;138 cases of Han nationality and 2 of other nationalities;38 cases of junior high school and below,34 of high school and technical secondary school,and 68 of ju-nior college and above;58 cases of adverse pregnancy history and 82 of non-adverse pregnancy history;11 cases of thyroid dis-ease family history and 129 of non-thyroid disease family history;16 cases of medication history and 124 of non-medication history during pregnancy;3 cases of progesterone history and 137 of non-progesterone history during pregnancy;8 cases of formaldehyde exposure history and 132 of non-formaldehyde exposure history during pregnancy;9 cases of radiation exposure history and 131 of non-radiation exposure history during pregnancy.Another 140 healthy newborn mothers were enrolled and set as control group,which aged 24-40 years old with mean age of 28.95 years old;gestational age of 34-41 weeks with mean of 39.13 weeks;131 cases of natural conception;pre-pregnancy body mass was 45.5-77.0 kg with mean body mass of 56.12 kg;number of births was 1-3 times with mean of 1.68 times;113 cases of spontaneous delivery and 27 of cesarean sec-tion;63 cases living in urban and 77 in rural;135 cases of Han nationality and 5 of other nationalities;16 cases of junior high school and below,32 of high school and technical secondary school,and 92 of junior college and above;79 cases of adverse pregnancy history and 61 of non-adverse pregnancy history;2 cases of thyroid disease family history and 138 of non-thyroid disease family history;3 cases of medication history and 137 of non-medication history during pregnancy;15 cases of proges-terone history and 125 of non-progesterone history during pregnancy;1 case of formaldehyde exposure history and 139 of non-formaldehyde exposure history during pregnancy;1 cases of radiation exposure history and 139 of non-radiation exposure histo-ry during pregnancy.The related factors of neonatal mothers were collected and used as the main research variables.The level of 25-hydroxyvitamin D[25(OH)D]in umbilical venous blood of neonates was detected by enzyme-linked immunosorbent assay.The FokI polymorphism of VDR in serum of neonatal mathers was determined by PCR-pyrosequencing.The univariate and multivariate Logistic regression analysis was used to study the correlation between maternal VDR FokI polymorphism and CH susceptibility.Results The genotype of VDR FokI locus in control group was tested by Hardy-Weinberg genetic balance test to evaluate the reliability of gene frequency estimation,and the results showed that the genotype distribution of FokI locus was in accordance with Hardy-Weinberg genetic balance law(x2=1.472,P＞0.05).The univariate analysis and multivariate Logistic regression analysis results showed that neonatal birth body mass,gestational age,Apgar score and maternal age,education level,residence,delivery mode,family history of thyroid disease,history of adverse pregnancy,history of progesterone during pregnan cy,history of medication during pregnancy,history of formaldehyde during pregnancy and history of radiation exposure were sig-nificantly correlated with neonatal CH(P＜0.05).The univariate and multivariate Logistic regression analysis results showed that maternal VDR FokI polymorphism was significantly associated with neonatal CH susceptibility,and genotype FF was sig-nificantly associated with increased risk of neonatal CH.There was significant difference in serum 25(OH)D levels between 2 groups of newborn in different genotypes of maternal VDR FokI locus(P＜0.015),the differences of FT3,FT4 and TSH lev-els were also statistically significant(P＜0.05),and serum 25(OH)D of newborn with maternal genotype FF was significantly lower than that of Ff and ff genotypes,FT3 and FT4 were also significantly lower than those of Ff and ff genotypes,and TSH was significantly higher than that of Ff and ff genotypes.Conclusion It is demonstrated that polymorphisms in FokI locus of maternal VDR may be correlated with susceptibility,and carrying homozygous FF genotype of FokI locus will increases the susceptibility of neonatal CH.
newbornscongenital hypothyroidismvitamin D receptor geneFokI locus polymorphismbiological mother
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