Batais Mohammed Ali, Almigbal Turky H, Shaik Noor Ahmad, Alharbi Fawaziah Khalaf, Alharbi Khalid Khalaf, Ali Khan Imran
Department of Family and Community Medicine, King Saud University, Riyadh.
Princess Al-Jawhara Al-Brahim Center of Excellence in Research of Hereditary Disorders, King Abdulaziz University, Jeddah.
Medicine (Baltimore). 2019 Jan;98(4):e14247. doi: 10.1097/MD.0000000000014247.
Familial hypercholesterolemia (FH) is a monogenic dominant inherited disorder of lipid metabolism characterized by elevated low-density lipoprotein levels, and is mainly attributable to mutations in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proportein convertase subtilisin/kexin type 9 (PCSK9) genes. Next-generation and exome sequencing studies have primarily involved genome-wide association analyses, and meta-analyses and next-generation studies examined a few single-nucleotide polymorphisms (rs151009667 and Val2095Glu) in the ApoB gene. The present study was conducted to investigate the association of APOB and patients with FH in a Saudi population.We genotyped 100 patients with FH and 100 controls for 2 polymorphisms in APOB using polymerase chain reaction-restriction fragment length polymorphism, followed by 3% agarose gel electrophoresis. The strength of the association between the genotype and allele frequencies with the risk of developing FH was evaluated. Clinical details and genotype analysis results were recorded.For the rs151009667 polymorphism, 18% of the CT genotypes were observed only in patients with FH. There was a positive association between CT and CC (odds ratio [OR] 45.07 [95% conflict of interest (CI), 2.67-759.1]; P = .0001) and between T and C (OR 87.8 [95% CI, 5.34-144.2]; P < .0001). However, no Val2095Glu mutations were found in patients with FH or controls. There was also no correlation between clinical characteristics and the rs151009667 polymorphism.In conclusion, we confirmed the association between the rs151009667 polymorphism and FH in a Saudi population. The Val2095Glu novel variant did not appear in either patients with FH or controls. Similar studies should be performed in different ethnic populations to rule out the role of this polymorphism in FH.
家族性高胆固醇血症(FH)是一种单基因显性遗传的脂质代谢紊乱疾病,其特征为低密度脂蛋白水平升高,主要归因于低密度脂蛋白受体(LDLR)、载脂蛋白B(APOB)和前蛋白转化酶枯草溶菌素9型(PCSK9)基因的突变。新一代测序和外显子组测序研究主要涉及全基因组关联分析,荟萃分析和新一代研究检测了ApoB基因中的一些单核苷酸多态性(rs151009667和Val2095Glu)。本研究旨在调查沙特人群中APOB与FH患者之间的关联。我们使用聚合酶链反应-限制性片段长度多态性对100例FH患者和100例对照进行APOB基因中2种多态性的基因分型,随后进行3%琼脂糖凝胶电泳。评估基因型和等位基因频率与发生FH风险之间的关联强度。记录临床细节和基因型分析结果。对于rs151009667多态性,仅在FH患者中观察到18%的CT基因型。CT与CC之间存在正相关(比值比[OR]45.07[95%可信区间(CI),2.67 - 759.1];P = 0.0001),T与C之间也存在正相关(OR 87.8[95%CI,5.34 - 144.2];P < 0.0001)。然而,在FH患者或对照中未发现Val2095Glu突变。临床特征与rs151009667多态性之间也无相关性。总之,我们在沙特人群中证实了rs151009667多态性与FH之间的关联。Val2095Glu新变体在FH患者或对照中均未出现。应在不同种族人群中进行类似研究,以排除该多态性在FH中的作用。