Contribuição dos níveis séricos de PCSK9 e seu polimorfismo rs505151 nos parâmetros do risco cardiometabólico de ribeirinhos da Amazônia

Abstract

Riverine communities in the Amazon have an increased incidence of cardiometabolic risk factors. Dysfunctions in the proprotein convertase subtilisin/kexin type 9 (PCSK9) activity and its gain-of-function polymorphisms (SNP) can contribute to hypercholesterolemia, insulin resistance, and inflammation. We investigated the role of serum levels of PCSK9 (below or above 220 ng/mL) and its rs505151 polymorphism in the incidence of metabolic syndrome (MetS) and cardiometabolic risk parameters presented by n=338 individuals living in the Tucuruí region (Pará, Brazil). We found higher levels of creatinine, non-HDL cholesterol, lipoprotein (a), LDL-c, and in its oxidized form, oxLDL, IL-6, and C-reactive protein in individuals with PCSK9 > 220 ng/mL. The AG/GG genotype (rs505151) was observed in 24,5% of individuals (n=83; p<0.0001) in agreement with Hardy-Weinberg equilibrium (p<0,0001). MetS occurred in 66% of individuals with the AG/GG genotype, in contrast to 52,5% of AA individuals (p=0,003). The presence of arterial hypertension was predictive of PCSK9 levels (p=0.017) and for the risk of simultaneously presenting the AG/GG genotype (p=0.007). PCSK9 levels > 220 ng/mL increased the overall cardiovascular risk of individuals without MetS, while the presence of the AG/GG genotype increased the cardiovascular risk score of individuals independent of other factors (p=0.015). Elevated serum levels of PCSK9 and the presence of its SNP rs505151 may contribute to hypercholesterolemia and thus promote other factors associated with cardiometabolic risk. In riverine populations, the high cardiometabolic risk presented appears to be associated with the favoring of a pro-inflammatory metabolic state, central adiposity, and arterial hypertension. Investigation of health parameters in neglected communities is necessary to help mitigate the spread of chronic non-communicable diseases, which are relevant to global morbidity and mortality but have an unequal impact on low-income populations.