Q192R polymorphism in the PON1 gene and familial hypercholesterolemia in a Saudi population

Abstract

BACKGROUNDFamilial hypercholesterolemia (FH) is an autosomal dominant condition characterized by abnormal levels of low-density lipoprotein (LDL) in the blood. FH is a risk factor for atherosclerosis and cardiovascular disease. The relationship between the paraoxonase 1 (PON1) gene, atherosclerosis and coronary artery disease has not been studied in Saudi patients.OBJECTIVETo investigate the genetic associations of the Q192R polymorphism in the PON1 gene with FH in Saudi patients.DESIGNCase-control study.SETTINGTertiary care center, Riyadh.METHODSTwo hundred Saudi patients were enrolled in this study, including 100 patients with FH and 100 healthy controls, during the period from January 2012 to March 2013. Serum was separated from coagulated blood (3 mL) and used for analysis of lipid profiles. Genomic DNA was isolated from anticoagulant-treated blood (2 mL). Genotyping for the Q192R polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism analysis, followed by 3% agarose gel electrophoresis.MAIN OUTCOME MEASUREThe strength of association between the Q192R polymorphism and FH in the Saudi population.RESULTSWe confirmed that QR versus QQ (odds ratio [OR]: 1.55; 95% confidence interval [CI]: 1.05–3.43; P=.03), QR+RR versus QQ (OR: 1.98; 95% CI: 1.13–3.49; P=.01), and R versus Q (OR: 1.68; 95% CI: 1.09–2.59; P=.01) in the Q192R polymorphism were associated with FH in the Saudi population.CONCLUSIONIn conclusion, the Q192R polymorphism in the PON1 gene is associated with FH in the Saudi population. Our results confirmed that the R allele, QR, and dominant model genotypes were associated with FH.LIMITATIONOnly a single variant (Q192R) was analyzed, and the medical and family histories of the patients were not known.

Screening of common genetic variants in the APOB gene related to familial hypercholesterolemia in a Saudi population

“…This study was performed according to the principles of the Declaration of Helsinki. As described in our prior publications, [7,14,15] 100 patients with FH were recruited from King Khalid University Hospital (KKUH) at KSU. Inclusion criteria were as follows: FH diagnosis made according to the Dutch group criteria [7] ; male or female; subjects who underwent regular checkups; and subjects with no endocrine, metabolic, chronic, and other diseases.…”

“…As described in our prior publications, [7,14,15] 100 patients with FH were recruited from King Khalid University Hospital (KKUH) at KSU. Inclusion criteria were as follows: FH diagnosis made according to the Dutch group criteria [7] ; male or female; subjects who underwent regular checkups; and subjects with no endocrine, metabolic, chronic, and other diseases. Exclusion criteria included the following: subjects with abnormal body mass index (BMI); subjects with diabetes; subjects with liver, renal, or thyroid disease or any other type of diseases; and subjects recruited outside the KKUH.…”

“…Genomic DNA was extracted from the EDTA blood using a commercial human DNA kit as described by Alharbi et al [7] To quantify genomic DNA, a NanoDrop spectrophotometer (Thermo Fischer Scientific, Waltham, MA) was used and primers were designed for the selected ApoB variants based on Radovica-Spalvina et al [3] The complete details of ApoB variants are listed in Table 1. The primers were designed using Primer 3 software.…”

“…Between patients with FH and controls, the association was tested using 2 independent sample t tests. [7] Genotype and allele frequencies between patients with FH and controls were assessed using Openepi software (version 2.3.1) to determine the odds ratios, χ 2 , and P values with and without Yates correction. Analysis of variance was also performed between the FH genotypes for rs151009667 and clinical characteristics.…”

“…FH-associated complications are common because of premature diagnosis and therapeutic interventions. [7] FH may be caused by a gain-of-function mutation in the LDL receptor ( LDLR ), apolipoprotein B ( APOB ), and pro-protein convertase subtilisin-Kexin type 9 ( PCSK9 ) genes. LDLR may suppress protein synthesis, which is translocated to the cell surface in monogenic mutations and by an additional mechanism that involves mutation affecting APOB , which encodes a key structural component of LDL and very low-density lipoprotein (VLDL).…”