The Roles Of Monoamine Neurotransmitters And Gene Polymorphism On Intelligence Of Children Exposed To Excessive Iodine

ObjectivesTo explore the effect of high iodine on children's intelligence quotient(IQ)and monoamine neurotransmitters and investigate the relationship between monoamine neurotransmitters and IQ,and probe into the moderating effect and interaction effect of gene polymorphisms of dopamine system in the effect of high iodine on intelligence,and to gain new findings in the relationship between high iodine and intellectual impairment and its biological mechanism.MethodsAdvisable iodine region(10 ?g/L? water iodine<150 ?g/L),No.1 iodine-excess region(150 ?g/L? water iodine<300 ?g/L)and No.2 iodine-excess region(water iodine?300 ?g/L)were selected from Binhai New Area and Jinghai District in Tianjin City according to the concentrations of iodine in drinking water.399 children aged from(7~12)years were chosen randomly to study by cluster sampling method.Intelligence quotient of children was measured by the Combined Raven's Test-The Rural in China.Morning urine of children was collected and urine iodine and fluoride levels were measured.Fasting venous blood in the morning of children were drawn to detect the levels of plasma monoamine neurotransmitters including dopamine(DA),5-hydroxytryptamine(5-HT),epinephrine(E)and norepinephrine(NE)by ELISA test.COMT NlaIII and DRD2/ANKK1 TaqIA polymorphism were detected by PCR-RFLP,and DAT 40 bp VNTR polymorphism was detected by PCR.Results1?There was no statistically significant difference in the sex distribution of children among the three regions(all P>0.05),while the age distribution had statistical significance.The average age of children in No.2 iodine-excess region was(10.21±0.81)years old which higher than that in advisable iodine region and No.1 iodine-excess region.2?The median urinary iodine of children in No.2 iodine-excess region was 476.30 ?g/L which higher than that in advisable iodine region(201.85 ?g/L)and No.1 iodine-excess region(209.15 ?g/L),and those differences had significance statistically(all P<0.05).The urine fluoride levels of children in No.2 iodine-excess region was 2.18(1.52~2.79)mg/L which higher than that in advisable iodine region and No.1 iodine-excess region,and those differences also had significance statistically(all P<0.05).3?The IQ score of children in No.2 iodine-excess region was 109.59,which was 4.93 point below the advisable iodine region and 5.98 below the No.1 iodine-excess region,and the differences were statistically significant(P<0.05).4?The level of DA in plasma of children in No.2 iodine-excess region was higher than that of DA in advisable iodine region and No.1 iodine-excess region,while the level of 5-HT of children in No.2 iodine-excess region was lower than that of 5-HT in other regions,and the differences were statistically significant(all P<0.05).While there was no significant difference in the levels of E and NE among the three regions(all P>0.05).5?Threshold analysis displayed there was a nonlinear relationship between iodine exposure and DA.The level of DA increased with the increase of urinary iodine in children with urinary iodine levels below 492.75 ?g/L.There is a threshold effect between DA and IQ.Every 1 ng/mL increment in the level of DA was associated with a raise of 0.1 in the IQ score when DA level below 80 ng/mL.In contrast,every 1 ng/mL increment in the level of DA was associated with a decline of 0.1 in the IQ score when DA level in the range of 80.0 to 359.8 ng/mL.There were no linear relationships or threshold effects between the urinary iodine and 5-HT,NE and E,respectively.And the linear correlation between intelligence quotient and 5-HT,NE and E were not found.6?The genotypes of COMT NlaIII and DRD2/ANKK1 TaqIA in the overall study samples accorded with Hardy-Weinberg equilibrium rule,and the genotypes and alleles frequencies of COMT NlaIII,DRD2/ANKK1 TaqIA and DAT 40 bp VNTR in the three regions were no statistic difference(all P>0.05),which indicated the selected samples had good population gene representativeness.7 ? There were no significant difference in IQ among children with different DRD2/ANKK1 and DAT genotypes(all P>0.05),except for COMT AA and GA genotypes(P<0.05).The age-COMT genotype interaction on intelligence had statistical significance(P<0.05).Compared with children aged 7~9,age-COMT gene interaction had greater impact on children aged 10~12,especially those with GA genotype had the lowest IQ score.8?High fluoride exposure had a certain degree of impairment on intelligence for those children with DRD2/ANKK1 TT genotype,Every 2.72 mg/L increment in the concentration of urinary fluoride was associated with a decline of 10.968 in the IQ score.The interaction between DRD2/ANKK1 gene and urinary fluoride was statistically significant(P<0.05),every 2.72 mg/L increment in the concentration of urinary fluoride was associated with a decline of 3.002 in the IQ score.There were no significant differences in the effects of high iodine or high fluoride on intelligence and the interaction between environment and gene in different genotypes of COMT NlaIII or DAT 40 bp VNTR(all P>0.05).ConclusionsThe metabolic dysfunction of DA and 5-HT occur in children exposed to excessive iodine,and a threshold effect exists between DA and intelligence quotient,the metabolic dysfunction of DA may be related to the decrease of intelligence quotient.However,the effect of high iodine on children's intelligence has not been found,nor has the moderating effect and interaction effect of gene polymorphisms of dopamine system.The DRD2/ANKK1 TaqIA gene polymorphism may increase the susceptibility to the deficits in IQ due to fluoride exposure,children with DRD2/ANKK1 TaqIA TT genotype has a higher risk for cognitive impairments after fluoride exposure.