Ethnic variations in mercury exposure from seafood consumption and the risk of Kawasaki disease in young children

Abstract

Kawasaki disease (KD) is an acute febrile illness predominately affecting children <5 years that can result in serious cardiovascular complications such as coronary artery lesion formation. The cause of KD remains unknown 50 years after Kawasaki first described the illness in Japan, while KD has since replaced rheumatic fever as the leading cause of acquired heart disease for children in the developed world. KD has become the most commonly diagnosed pediatric vasculitis with the highest incidence rates of KD reported from East Asian countries such as Japan, Korea, and Taiwan. Even when residing in Western nations, East Asian children still have 10 to 20 times the risk of developing KD than children of other ethnicities. Speculation that genetic differences between ethnic groups account for the ethnic disparity in KD rates led to the discovery and confirmation of numerous susceptibility loci, although these risk alleles only appear to confer risk passively to the currently unknown environmental triggers of KD. Previously, we described how ITPKC susceptibility in KD patients would render these individuals vulnerable to mercury (Hg)‐induced autoimmunity through the induction of intracellular calcium release with downstream effects upon cell signaling, immune proliferation, and gene expression via the Ca2+/NFAT pathway. This led us to hypothesize that the ethnic disparities in KD risk may be accounted for by variations in Hg exposure rates, particularly from significant differences in total methylmercury (MeHg) intake from seafood. We examined two separate cohorts that were nationally representative of either KD hospitalization rates or toxic metal concentrations in the blood in our initial investigations. Our results demonstrated that increasing ethnic KD risk between Caucasian, Hispanic, Black, and Asian children was significantly associated with average blood levels and detection rates of Hg or cadmium (Cd) but not lead (Pb), manganese (Mn), or selenium (Se). In our most recent investigations using the same two datasets, we observed that ethnic KD risk was significantly associated with increasing consumption of total fish and seafood but not shellfish. Further examinations by Hg type demonstrated that MeHg from seafood is the primary source of blood Hg in children, while average blood MeHg levels but not inorganic or ethylmercury were significantly associated with increasing ethnic KD risk. Lastly, ethnic KD risk was significantly associated with molar ratios of Hg and Se in the blood that are indicative of seafood consumption. We conclude that Hg exposure particularly from seafood consumption may increase susceptibility for the development of KD in young children or trigger the disease, itself. However, our hypothesis requires determinations of blood Hg levels and cumulative Hg exposure such as from dietary seafood intake in KD patients, which are currently lacking and that we are presently examining.Support or Funding InformationNone