Genetics
CETP mutations are identified for the first time in South Indian patients with familial hypercholesterolemia (Clin Chim Acta 2022)
Original title: Targeted exome sequencing in South Indian patients with Familial hypercholesterolemia
In the first targeted exome sequencing study of familial hypercholesterolemia in South India, researchers analysed 54 patients (31 index cases plus 23 extended family members) categorised by Dutch Lipid Clinic Network Criteria, using a 23-gene lipid-metabolism panel. Mutations were found in 12 of the 23 genes, and CETP, along with APOA5, EPHX2 and SREBP2, was identified for the first time in Indian familial hypercholesterolemia patients, alongside a novel LDLR frameshift mutation, together explaining mutations in 28 (52%) of subjects. Notably, about 73% of clinically identified familial hypercholesterolemia patients carried no mutations in the classical genes LDLR, apoB or PCSK9, underscoring the polygenic nature of the disease and the value of broader exome sequencing panels including CETP in genetically diverse populations.
Original abstract
Background: Familial hypercholesterolemia (FH) is an autosomal dominant genetic disorder with elevated LDL-C levels which can ultimately lead to premature Coronary Artery Disease (CAD).
Objectives: In presence of limited genetic data on FH in India, the present study was aimed to determine the mutation spectrum in Indian FH patients using a targeted exome sequencing.
Methods: 54 FH cases (31 index cases + 23 extended family members) were categorized according to Dutch Lipid Clinic Network Criteria (DLCNC). Targeted exome sequencing was performed using 23 gene panel associated with lipid metabolism.
Results: All subjects showed the presence of family history of CAD, 38(70%) patients had corneal arcus whereas only 06(11%) subjects had xanthomas. As per the DLCNC, definite, probable, possible and unlikely FH were 48%, 30%, 11% and 11% respectively. Mutations were observed in 12 of the 23 gene panel with CETP, APOA5, EPHX2 and SREBP2 genes were identified for the first time in Indian FH patients. All 19 mutations including a novel frame-shift mutation in LDLR gene were reported for the first time in Indian FH patients. These mutations were identified in 28(52%) subjects and interestingly ∼73% of the clinically identified FH patients didn't harbour mutations in FH classical genes (LDLR, ApoB, PCSK9).
Conclusion: This is the first study in the South Indian FH patients to perform targeted exome sequencing. Absence of mutations in the FH classical genes strongly indicates the polygenic nature of FH, further underscoring the importance of targeted exome sequencing for identifying mutations in genetically diverse Indian population.
ancestryfamilial hypercholesterolaemiagenetics
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.