Exploring the LDL-cholesterol raising SNPs gene scores for improved screening of polygenic familial hypercholesterolemia in Indian population: Pilot study

• Published in: Gene reports 2023-03, Vol.30, p.101735, Article 101735
• Main Authors: ArulJothi, K.N., Kumaran, K., Abirami, Suruthi, Kirubakaran, Rangasamy, Devi, Arikketh
• Format: Article
• Language: English
• Subjects: Cardiovascular disease; Familial hypercholesterolemia; Gene score; LDL cholesterol; Polygenic; Polymorphism
• ISSN: 2452-0144; 2452-0144
• DOI: 10.1016/j.genrep.2022.101735

Familial hypercholesterolemia is one of the major causes of cardiovascular diseases, mainly characterized by increased LDL and total cholesterol levels in the blood. It has been established by numerous Genome-Wide Association studies that there are about 64 gene loci that play a significant role in lipid metabolism. These gene loci are considered to be the cause of polygenic FH, in addition to the three major FH-causing genes LDLR, APOB, and PCSK9. Studies by UK-based research groups established that only 6 SNPs are involved in increasing/elevating the LDL cholesterol in the Caucasian population. Based on these findings, we initiated the gene score study using 6 LDL-C-raising SNPs for the first time in the Asian Indian population. Patients with a clinical diagnosis of hypercholesterolemia who did not show any mutations in the major genes were screened for other LDL cholesterol-raising SNPs risk alleles. The subjects with normal lipid profiles and no CVD history were considered a control group in this study. The results revealed that the FH/M- samples had higher mean LDL-C gene risk scores than the controls, although statistically not significant. It is evident from these reports that the Asian cohort needs a separate large population study on this aspect to determine whether to use these gene scores for the prediction of CVD risk or to assess which of these LDL-C-associated SNPs play a crucial role in increasing LDL-C in the Asian population. •Monogenic FH mutation detection is low in the Indian population.•Polygenic FH is least explored in the Indian population.•The LDL-C SNP gene scores can be used to detect the polygenic FH.•6 LDL-C SNPs tested in this study were unable to distinguish the polygenic FH.•Other LDL-C SNPs need to be tested further.