STUDY OF THE DOUBLE POLYMORPHISM (THR 555ILE) AND (GLU568PRO) OF THE CORIN GENE AS A RISK FACTOR FOR ARTERIAL HYPERTENSION IN A POPULATION OF AFRICAN DESCENT IN GUADELOUPE

Overview

Cardiovascular disease (CVD) mortality is the leading cause of death in high-income countries (particularly the United States), accounting for 23.1% of all deaths It has been established over several decades that hypertension disproportionately affects African Americans, compared with Americans of European descent:Hypertension occurs more often, at an earlier age , with greater severity , and is associated with an approximately 3-fold higher probability of death .There is also poorer control of hypertension despit e similar treatment In African Americans, CVD morbidity and mortality are compounded by the higher prevalence of T2DM, obesity, CKD, stroke, and heart failure . Despite advances in the identification of risk factors and the availability of effective treatment in hypertension, CVD disparities, persist among African Americans and are expected to increase in the future, particularly in younger age groups. Although various environmental and social factors certainly contribute to these disparities, a genetic basis, involving numerous "candidate" genes, is most often asserted in the literature . One of these is the Corin gene (Pan et al, 2002) which codes for the Corin protein.The latter plays a pivotal role in cardiometabolic pathophysiology through its role in the activation of natriuretic peptides .Natriuretic peptides (ANP and BNP) have a major role in the regulation of blood pressure through their vasodilatory and diuretic action. They have a lusotropic action, inhibit the renin angiotensin system, and are involved in energy metabolism (increased lipolysis and insulin secretion). They also have an anti-fibrotic, anti-proliferative, anti-inflammatory and anti-thrombotic action.The Corin gene of 244109pb has many variants that produce an inefficient protein with the corollary of the appearance of metabolic and cardiovascular pathologies in the first rank of which the HTA, the cardiac insufficiency and the renal insufficiency .Recently, a double polymorphism of the Corin gene consisting of 2 SNPs (single nucleotide polymorphisms) on the same allele of the Corin gene (I555/P568) has been reported. This allele is present in the heterozygous state in 12% of African Americans but is extremely rare in Americans of European descent (\<0.5%).This double polymorphism (I555/P568) has been shown to be responsible for an approximately 70% reduction in the ability of the mutated Corin protein to convert proANP or proBNP to the active form. In addition, the I555(P568) allele of Corin protein is associated with an increased risk of hypertension and concentric cardiac hypertrophy The corin allele (I555/P568) is reported to be associated with poorer response to validated heart failure therapy and a higher risk of death or hospitalization for heart failure . In Guadeloupe, where the population is predominantly of African descent.Cardiovascular disease is the leading cause of mortality.The prevalence of hypertension is 39% and more than 50% after 50 years of age . It has increased by 10% in 10 years in Guadeloupe. In France, where the prevalence of hypertension is 31%, it has increased by only 5% over the same period. Heart failure is the main cause of admission to the cardiological emergency room of the University Hospital (49%) with a mortality of 37% at 6 months. Hypertension is the first risk factor associated with heart failure (80%).To date, there are no studies on corin gene polymorphisms in Guadeloupe. Following the example of work already done in the African American population, we propose to study the role of the double polymorphism (I555/P568) in the determinism of hypertension in the population of African descent in Guadeloupe.