الملخص الإنجليزي
Background: Familial hypercholesterolemia (FH) is characterized by elevated levels of low-density lipoprotein (LDL) in the blood. FH previously thought to have a monogenic basis, but can also be caused by building up of common small-effect LDL-C-raising alleles (polygenic). The Global Lipid Genetic Consortium (GLGC) meta-analysis of genome-wide association studies identified several loci where common variants affect LDL-C concentration. Objective: The aim of this work was to determine polygenic score in FH patients, assess the utility of 6-SNP polygenic score or 12-SNPs polygenic score in identification of polygenic FH, and to study the contribution of polygenic effect on LDL-C before and after lipid lowering therapy.
• Methods: The study subjects were obtained from a previously ongoing study on patients with FH. Total of 93 extracted DNA from patients and control subjects. The data collected from Sultan Qaboos University Hospital (SQUH). The genotypes of the 12 SNPs used to calculate the polygenic score, and then data analysis was done using statistical analysis tests. Results: Positive correlations found between the 12-SNPs and the 6-SNPs polygenic score in individuals (Pearson's R-Coefficient =0.89, P-value <0.0001). LDL-C SNP 12 score of FH/M+ group, (0.98 (SD 0.13]) was statistically not significant to the healthy control group (0.97 (SD 0.23]), P-value =0.858. Also, the FH/M- group (1.02 [SD 0.11]) compared to the control group (0.97 [SD 0.23]), P-value =0.2204. As the FH/M- group and FH/M+ group showed no significant difference in both groups was, P-value = 0.2. In conclusion, the utility of 6-SNPs polygenic score in measurement of polygenic markers for FH, adds cost and effort-effective approach compared to 12 SNPs polygenic score. Also the reported GLGC weights of LDL-C failed to differentiate between polygenic familial hypercholesterolemia and monogenic forms in the Omani population. Future studies are required to establish LDL-C polygenic score on Arabic population. Keywords: Familial Hypercholestrolemia, polygenic, SNP
