KEAP1 polymorphisms and neurodevelopmental outcomes in children with exposure to prenatal MeHg from the Seychelles Child Development Study Nutrition Cohort 2

• Published in: Neurotoxicology (Park Forest South) 2023-12, Vol.99, p.177-183
• Main Authors: de Paula, Helena Korres, Love, Tanzy M, Pineda, Daniela, Watson, Gene E, Thurston, Sally W, Yeates, Alison J, Mulhern, Maria S, McSorley, Emeir M, Strain, J J, Shamlaye, Conrad F, Myers, G J, Rand, Matthew D, van Wijngaarden, Edwin, Broberg, Karin
• Format: Article
• Language: English
• Subjects: Animals; Child Development; Clinical Medicine; Female; Humans; Infant; Kelch-Like ECH-Associated Protein 1 - genetics; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Mercury - adverse effects; Mercury - toxicity; Methylmercury Compounds - adverse effects; Methylmercury Compounds - toxicity; Neurologi; Neurology; NF-E2-Related Factor 2 - genetics; Pediatrics; Pediatrik; Pregnancy; Prenatal Exposure Delayed Effects - genetics; Psychiatry; Psykiatri; Seychelles
• ISSN: 0161-813X; 1872-9711; 1872-9711
• DOI: 10.1016/j.neuro.2023.10.008

Humans differ in the metabolism of the neurotoxicant methyl mercury (MeHg). This variation may be partially due to variation in genes encoding the transcription factor Nuclear factor E2-related factor 2 (NRF2) and its negative regulator Kelch-like ECH-Associated Protein 1 (KEAP1), which regulate glutathione and related transporter and antioxidant proteins that play a role in the metabolism and neurotoxicity of MeHg. To elucidate a potential risk from genetic variation in NFE2L2 (encoding NRF2) and KEAP1 toward prenatal mercury exposure and child neurodevelopmental outcomes at 20 months and 7 years of age in a population with variable prenatal exposure to MeHg from maternal fish consumption. Nutrition Cohort 2 is a mother-child cohort in the Republic of Seychelles. Children were genotyped for NFE2L2 (rs2364723, rs13001694) and KEAP1 (rs8113472, rs9676881) polymorphisms (N = 1285 after removing siblings). Total mercury (Hg) was measured in cord blood as a biomarker for prenatal MeHg exposure. Child neurodevelopmental outcomes included the Bayley Scales of Infant Development II administered at 20 months of age, and outcomes across multiple neurodevelopmental domains from 14 tests administered in children and 3 instruments completed by parents when children were 7 years of age. The mean cord blood MeHg concentration was 34 (95% CI 11, 75) µg/L. None of the four polymorphisms had a significant association (p