Fara, Isna Rahmia and Bahrudin, Bahrudin and Mundhofir, Farmaditya EP (2014) MUTATION IDENTIFICATION OF ABCA1 GENE IN SUBJECTS WITH LOW LEVEL OF HIGH DENSITY LIPOPROTEIN IN SEMARANG. Masters thesis, Universitas Diponegoro.

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Abstract

Background: The crucial part of HDL metabolism for protection against development of atherosclerosis is generally attributed to its role in reverse cholesterol transport, and ABCA1 gene is a key element to this process. ABCA1 gene mutation comprises about 15% of low HDL-C level cases. The purpose of this study was to identify the predicted pathogenic mutation of ABCA1 gene in subject with low level of high density lipoprotein.

Methods: Blood samples were taken from 42 subjects with low HDL-C level (<40mg/dL). Analysis of mutation screening for ABCA1 gene was done by using high resolution melting (HRM) technique. The aberrant samples were confirmed by DNA sequencing. Alamut software was used to predict pathogenic mutation. Results: Subjects were consisted of 24 (57,1%) males and 18 (42.9%) females. The secondary risk factors which may influence the level of HDL-C were age, gender, smoking, diabetes mellitus, body mass index, menopause, hypertension, and CAD were not significant different to HDL-C level at each group. Nine polymorphisms were identified. One variant found in 5’UTR known was c.-76dup (rs1799777). Three variants were identified in intron, i.e., c.+378G>C (rs1800978), c.814-14dup (rs2067484) and c.1892+24T>A (rs4743763). Four variants found as synonymous substitutions were c.936C>T (rs2274873), c.948G>A (rs2246841), c.2040C>A (rs2853579), and c.5586G>A. A variant c.2311G>A (rs2066718) was predicted deleterious. We found no symptoms or other similar condition from the family in Pedigree analysis of this subject. The c.5586G>A was a novel variant, while the rest were already reported in the SNP database.

Conclusion: Nine of ABCA1 variant were identified in this study, it consists of 8 reported SNP and 1 novel variant c.5586G>A. One variant known as missense substitution c.2311G>A was predicted pathogenic. No risk factors were significant different to influence the low level of HDL-C.

Keywords: Low HDL-C level, ABCA1 gene, HRM, Sequencing

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