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Introduction: Corneal arcus and eyelid xanthelasma are the common ocular findings but not exclusively found in familial hypercholesterolaemia (FH) patients. Low density lipoprotein receptor (LDLR) gene is the one of the most common genes investigated in FH. There is no study predicting ocular manifestations with genetic variations of the LDLR gene.
Purpose: To associate common ocular manifestations of FH and LDLR gene in Malays.
Material and methods: A cross-sectional study involving 50 unrelated Malay patients with FH were recruited. FH was diagnosed based on Dutch Lipid Clinic Network diagnostic criteria. The right eye was examined for eyelid xanthelasma and corneal arcus, while mean retinal nerve fibre layer thickness (RNFL) was assessed using Heidelberg retinal tomography II. Venepuncture was performed and genomic deoxyribonucleotide acid (DNA) was extracted. LDLR gene variations were screened using denaturing high-performance liquid chromatography and confirmed through DNA sequencing.
Results: Corneal arcus was detected in 86.0% of patients, while eyelid xanthelasma was detected in 2.0% of patients. Mean RNFL thickness was 254.16 μm (SD: 60.67 μm). LDLR gene variations were identified in 32 patients (64.0%), including 5 mutations and 9 single nucleotide polymorphisms (SNPs). Two novel mutations were detected: c.1705+117T>G and p.Asp139His. There was significant association between genotype frequency of LDLR variations c.940+36G>A, p.Glu201Lys and p.Asp304Asn with FH, p.Glu201Lys with corneal arcus, and p.Cys255Ser and c.1705+117T>G with mean RNFL thickness.
Conclusion: LDLR gene variations were not uncommon in Malay patients with FH. Two novel variations, c.1705+117T>G and p.Asp139His, were identified. LDLR gene is a potential predictor genetic marker for corneal arcus in Malay patients with FH. c.1705+117T>G is associated with thinner mean RNFL thickness.