Background: The identification of the critical regions within angiotensin-converting enzyme (ACE) gene which predict hypertension and/or influence ACE activity would have significant implications for precision medicine. Studies investigating the association of ACE gene polymorphisms and the risk of developing hypertension have yielded inconsistent results.
Objective: The aim of the study is to identify single nucleotide polymorphisms (SNPs) or haplotype markers in exon 13 of ACE gene and their association with essential hypertension in a sample of Sudanese population.
Methods: Amplified fragments of 550bp across exon 13 of ACE gene were outsourced to the Macrogen Company, Seoul, South Korea for sequencing. Finch TV program was used to view the chromatogram. Gene sequences were translated into amino acid sequence, using GeneMark version 4.25. The structural effect of a point mutation in a protein sequence was analyzed using PROJECT HOPE online website. Linkage disequilibrium between polymorphic variants was determined using Haploview v4.2.
Results: Seven polymorphisms of ACE gene were identified in the sequenced fragments: four exonic SNPs (Rs4316, rs4317, rs4318 and one unreported SNP); an intronic SNP (rs12720723); one SNP at the intronic-exonic boundary site (rs4320); and an intronic I/D (rs4319). Haplotype analysis identified two blocks within 550bp spanning area of the ACE gene. Both blocks were composed of six SNPs: rs12720723; unreported SNP; rs4316; rs4317; rs4318 and rs4319. Each block consisted of five haplotype structures. Block 1 included B1-H1 (GCC), B1-H2 (ACC), B1-H3 (GCT), B1-H4 (GAT) and B1-H5 (AAT), whereas block 2 included B2-H1 (TAC), B2-H2 (CGC), B2-H3 (TAA), B2-H4 (CAC) and B2-H5 (TGC). Rs4317 and rs4318 were in moderate linkage disequilibrium (LD) (D’ value=0.69) among hypertensive patients. Rs4316; rs4319 and rs4320 were in moderate to high LD and displayed relatively high MAF among hypertensive participants.
Conclusion: The results of our study suggest that the 3 SNPs within exon 13 of the ACE gene (rs4316, rs4319 and rs4320) could be genetic markers for developing hypertension as evidenced by the high LD and MAF observed in hypertensive participants. Moreover, rs4318 being in LD with rs4317 could highlight the importance of block 2 in predicting hypertension among blacks.
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