Methylmercury exposure, PON1 gene variants and serum paraoxonase activity in Eastern James Bay Cree adults.
There is growing evidence that cardiovascular health can be affected by exposure to methylmercury (MeHg), by a mechanism involving oxidative stress. Paraoxonase 1 (PON1) is a high-density lipoprotein-bound enzyme that hydrolyzes toxic oxidized lipids and protects against cardiovascular diseases. Evidence from in vitro studies indicates that MeHg can inhibit PON1 activity but little is known regarding this effect in humans. We investigated whether increased blood mercury levels are associated with decreased serum PON1 activity in Cree people who are exposed to MeHg by fish consumption. We conducted a multi-community study of 881 Cree adults living in Eastern James Bay communities (Canada). Multivariate analyses considered sociodemographic, anthropometric, clinical, dietary and lifestyle variables and six PON1 gene variants (rs705379 (-108C/T), rs662 (Q192R), rs854560 (L55M), rs854572 (-909C/G), rs854571 (-832C/T) and rs705381 (-162C/T)). In a multiple regression model adjusted for all potential confounding factors and the rs854560 PON1 variant, a statistically significant MeHg*rs705379 interaction was observed. Blood mercury levels were inversely associated with serum PON1 activities in individual homozygous for the -108T allele (P=0.009). Our results suggest a gene-environment interaction between the rs705379 polymorphism and MeHg exposure on PON1 activity levels in this aboriginal population. This finding will need to be replicated in other population studies.
Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada.
Olivia
O
Drescher
1] Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada [2] Département de médicine sociale et préventive, Université Laval, Québec, Quebec, Canada.
Eric
E
Dewailly
1] Département de médicine sociale et préventive, Université Laval, Québec, Quebec, Canada [2] Centre des maladies du sein Deschênes-Fabia, Centre de recherche du CHU de Québec, Québec, Quebec, Canada.
Caroline
C
Diorio
Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada.
Nathalie
N
Ouellet
Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada.
Elhadji Anassour Laouan
EA
Sidi
1] Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada [2] Département de médicine sociale et préventive, Université Laval, Québec, Quebec, Canada.
Belkacem
B
Abdous
Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada.
Beatriz
B
Valera
1] Axe Santé des populations et pratiques optimales en santé, Centre de recherche du CHU de Québec, Québec, QC, Canada [2] Département de médicine sociale et préventive, Université Laval, Québec, Quebec, Canada [3] Laboratoire de toxicologie, Institut national de santé publique du Québec, Québec, Quebec, Canada.
Pierre
P
Ayotte
D000293:Adolescent; D000328:Adult; D043303:Aryldialkylphosphatase / Q000097:blood* / Q000235:genetics*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases; D003920:Diabetes Mellitus / Q000453:epidemiology; D059647:Gene-Environment Interaction; D005838:Genotype; D006801:Humans; D008055:Lipids / Q000097:blood; D008767:Methylmercury Compounds / Q000097:blood*; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011792:Quebec / Q000453:epidemiology; D012307:Risk Factors; D017747:Seafood / Q000009:adverse effects* / Q000706:statistics & numerical data; D012643:Selenium / Q000097:blood; D011795:Surveys and Questionnaires; D055815:Young Adult
D015415:Biomarkers; D008055:Lipids; D008767:Methylmercury Compounds; C030957:methylmercury II; D043303:Aryldialkylphosphatase; D012643:Selenium