SUN-561 Genetic Variants Related to Familial Hypercholesterolemia in Clusters from Minas Gerais - a Southeast State of Brazil

Familial Hypercholesterolemia (FH) is an autosomal dominant genetic disease, characterized by high levels of the cholesterol fraction present in low density lipoprotein (LDLc). FH is associated to early atherosclerotic coronary disease, which can result in acute myocardial infarction and angina pectoris. Clinical diagnosis of FH in adults is based on elevated LDLc levels ≥ 4,9 mmol/L and total cholesterol (TC) ≥ 7,5 mmol/L; in untreated children and adolescents LDLc ≥ 4,0 mmol/L and TC ≥ 6,7 mmol/L, associated or not with physical signs (xanthomas, corneal arch). In Brazil, it is estimated that there are from 402,000 to 607,000 cases of FH. This study aimed to evaluate the genetic variants related to FH in a small region from Minas Gerais, a southeast state in Brazil. Fifteen index cases (IC) were selected in two cities (Bom Despacho and Moema), that comprise 1.416 km(2) in that region. Family members (n=69) were also selected, when possible, for genetic analysis, which was carried out by the NGS (Next Generation Sequencing) method, using Illumina® technology. Six different genetic variants were identified: 1) Pathogenic variants in LDLR gene - Asp224Asn in 74 individuals (10 IC); Cys34Arg in 1 individual (1 IC); Asp601His in 2 individuals (1 IC); and Ser854Gly in 2 individuals (1 IC); 2) Variant of uncertain significance (VUS) in APOB gene - Met499Val in 1 individual (1 IC); and 3) VUS in PCSK9 gene - Arg237TRP in 4 individuals (1 IC). All variants were identified in heterozygosis. The data suggest that the high prevalence of FH in that small region in Brazil is related to inbreeding observed in the families investigated. In addition, a founder effect could also contribute to the elevated frequency of LDLR gene variants, mainly Asp224Asn. The data show the importance of molecular investigation on clinical conduct in FH Brazilian patients and their family members.