Spectrum of mutations of familial hypercholesterolemia in the 22 Arab countries

• Published in: Atherosclerosis 2018-12, Vol.279, p.62-72
• Main Authors: Alhababi, Dalal, Zayed, Hatem
• Format: Article
• Language: English
• Subjects: Adaptor Proteins, Signal Transducing - genetics; Apolipoprotein B-100 - genetics; Arab countries; Arabs - genetics; Familial hypercholesterolemia; Genetic Association Studies; Genetic Predisposition to Disease; Genotype-phenotype correlation; Humans; Hyperlipoproteinemia Type II - diagnosis; Hyperlipoproteinemia Type II - ethnology; Hyperlipoproteinemia Type II - genetics; LDL-C LDLR; LDLRAP1; Middle East - epidemiology; Mutation; PCSK9; Phenotype; Prevalence; Proprotein Convertase 9 - genetics; Receptors, LDL - genetics; Risk Factors
• ISSN: 0021-9150; 1879-1484
• DOI: 10.1016/j.atherosclerosis.2018.10.022

Familial hypercholesterolemia (FH) is an inherited genetic disorder of lipid metabolism characterized by a high serum LDL-cholesterol profile and xanthoma formation, and FH increases the risk of premature atherosclerosis and cardiovascular disease (CVD). Mutations in the low-density lipoprotein (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin 9 (PCSK9), and LDLRAP1 genes have been associated with FH. Although FH is a major risk for CVD, the disease prevalence and its underlying molecular basis in the 22 Arab countries are still understudied. This study aimed to analyze all peer-reviewed studies related to the prevalence of FH and its causative mutations in the 22 Arab countries. We searched five literature databases (Scopus, Science Direct, Web of Science, PubMed, and Google Scholar) from inception until June 2018, using all possible search terms to capture all of the genetic and prevalence data related to Arab patients with FH. A total of 5,484 titles and abstracts were identified; 51 studies met our inclusion criteria for the final systematic review. Fifty-one mutations in Arab patients with FH were identified in only eight Arab countries; 47 were identified in the LDLR gene, two in the PCSK9 gene, and two in LDLRAP1 gene. Twenty mutations in the LDLR gene were distinctive to Arab patients. A few studies reported prevalence estimates, ranging from 0.4% to 6.8%. This is the first systematic review to dissect the up-to-date status of the genetic epidemiology of Arab patients with FH. It seems that FH is underdiagnosed and that its prevalence is understudied due to the dearth of published information about Arab patients with FH. Therefore, there is a need for well-controlled genetic epidemiological studies on Arab patients with FH. •Consanguinity is common among Arab patients with FH.•High consanguinity among Arabs create unique founder mutations to Arab patients with FH.•Founder mutations are responsible for a large number of Arab patients with FH.•Arab patients with FH have distinctive clinical and genetic profiles.•There is a dearth of studies related to the genetic epidemiology of FH in Arab countries.