| 1. |
- Llop, Sabrina, et al.
(författare)
-
CYP3A genes and the association between prenatal methylmercury exposure and neurodevelopment
- 2017
-
Ingår i: Environment International. - : Elsevier BV. - 0160-4120 .- 1873-6750. ; 105, s. 34-42
-
Tidskriftsartikel (refereegranskat)abstract
- Background Results on the association between prenatal exposure to methylmercury (MeHg) and child neuropsychological development are heterogeneous. Underlying genetic differences across study populations could contribute to this varied response to MeHg. Studies in Drosophila have identified the cytochrome p450 3A (CYP3A) family as candidate MeHg susceptibility genes. Objectives We evaluated whether genetic variation in CYP3A genes influences the association between prenatal exposure to MeHg and child neuropsychological development. Methods The study population included 2639 children from three birth cohort studies: two subcohorts in Seychelles (SCDS) (n = 1160, 20 and 30 months of age, studied during the years 2001–2012), two subcohorts from Spain (INMA) (n = 625, 14 months of age, 2003–2009), and two subcohorts from Italy and Greece (PHIME) (n = 854, 18 months of age, 2006–2011). Total mercury, as a surrogate of MeHg, was analyzed in maternal hair and/or cord blood samples. Neuropsychological development was evaluated using Bayley Scales of Infant Development (BSID). Three functional polymorphisms in the CYP3A family were analyzed: rs2257401 (CYP3A7), rs776746 (CYP3A5), and rs2740574 (CYP3A4). Results There was no association between CYP3A polymorphisms and cord mercury concentrations. The scores for the BSID mental scale improved with increasing cord blood mercury concentrations for carriers of the most active alleles (β[95% CI]: = 2.9[1.53,4.27] for CYP3A7 rs2257401 GG + GC, 2.51[1.04,3.98] for CYP3A5 rs776746 AA + AG and 2.31[0.12,4.50] for CYP3A4 rs2740574 GG + AG). This association was near the null for CYP3A7 CC, CYP3A5 GG and CYP3A4 AA genotypes. The interaction between the CYP3A genes and total mercury was significant (p < 0.05) in European cohorts only. Conclusions Our results suggest that the polymorphisms in CYP3A genes may modify the response to dietary MeHg exposure during early life development.
|
|
| 2. |
- Yeates, Alison J., et al.
(författare)
-
PUFA status and methylmercury exposure are not associated with leukocyte telomere length in mothers or their children in the seychelles child development study
- 2017
-
Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 147:11, s. 2018-2024
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Leukocyte telomere length (TL) is associated with age-related diseases and early mortality, but there is a lack of data on the determinants of TL in early life. Evidence suggests that dietary intake ofmarine n-3 (v-3) polyunsaturated fatty acids (PUFAs) is protective of telomere attrition, yet the effect of methylmercury exposure, also found in fish, on TL is unknown. Objective: The aim of this study was to investigate the associations between prenatal PUFA status, methylmercury exposure, and TL in mothers and children in the SCDS (Seychelles Child Development Study), for whom fish consumption is high. Methods: Blood samples collected from 229 mothers (at 28 wk gestation and delivery) and children (at 5 y of age) in the SCDS first nutrition cohort were analyzed for PUFA concentrations. Prenatal mercury was measured in maternal hair collected at delivery. Postnatalmercury was alsomeasured in children's hair samples with the use of a cumulativemetric derived from values obtained at 3-5 y of age. Relative TL wasmeasured in blood obtained from mothers at delivery, in cord blood, and in children at 5 y of age by quantitative polymerase chain reaction. Linear regression models were used to investigate the associations between PUFA status, methylmercury exposure, and TL. Results: Neither prenatal PUFA status or methylmercury exposure was associated with TL of the mother or child or with TL attrition rate. However, a higher prenatal n-6:n-3 PUFA ratiowas significantly associated with longer TLs in the mothers (β = 0.001, P = 0.048). Child PUFA status andmethylmercury exposurewere not associated with child TL. However, higher family Hollingshead socioeconomic status (SES) scores at 9 mo of agewere significantly associatedwith longer TLs in cord blood (β = 0.005, P=0.03). Conclusions: We found no evidence that PUFA status or methylmercury exposure are determinants of TL in either the mother or child. However, our results support the hypothesis that family SES may be associated with child TL.
|
|
