Polymorphisms in Exon 13 of Angiotensin-Converting Enzyme Gene among Hypertensive Patients in Sudan


  •   R. T. Osman

  •   D. A. Hassan

  •   M. I. Elamin

  •   M. Elamin

  •   D. Mursi

  •   M. A. M. Salih


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.

Keywords: ACE gene, essential hypertension, haplotype view, linkage disequilibrium, polymorphisms


Lifton RP. Molecular genetics of human blood pressure variation. Science. 1996; 272(5262): 676-80.

Adigun AQ, Ishola DA, Akintomide AO, Ajayi AAL. Shifting trends in the pharmacologic treatment of hypertension in a Nigeria tertiary hospital: a real-world evaluation of the efficacy, safety, rationality, and pharmaco-economics of old and newer antihypertensive drugs. J Hum Hypertens. 2003; 17: 277–285.

Opie LH, Seedat YK. Hypertension in sub-Saharan African populations. Circulation. 2005; 112: 3562–3568.

Beheiry HM, Abdalla AA, Fahal NA, Mohamed MI, Ibrahim DA, Medani SA, et al. May Measurement Month 2018: an analysis of blood pressure screening results from Sudan, European Heart Journal Supplements. 2020, 22: H122–H124.

Maluf-Meiken LC, Fernandes FB, Aragão DS, Ronchi FA, Andrade MC, Franco MC, et al. N-domain isoform of Angiotensin I converting enzyme as a marker of hypertension: populational study. Int J Hypertens. 2012; 2012: 581780.

Ji LD, Zhang LN, Shen P, Wang P, Zhang YM, Xing W, et al. Association of angiotensinogen gene M235T and angiotensin-converting enzyme gene I/D polymorphisms with essential hypertension in Han Chinese population: a metaanalysis. J Hypertens. 2010; 28: 419–428.

Zarouk WA, Hussein IR, Esmaeil NN, Raslan HM, Reheim HAA, Moguib O, et al. Association of angiotensin converting enzyme gene (I/D) polymorphism with hypertension and type 2 diabetes. Bratisl Lek Listy. 2012; 113(1): 14–18.

He Q, Fan C, Yu M, Wallar G, Zhang ZF, Wang L, et al. Associations of ACE gene insertion/deletion polymorphism, ACE activity, and ACE mRNA expression with hypertension in a Chinese population. PLoS One. 2016; 11(5): e0156564.

Mengesha HG, Petrucka P, Spence C, Tafesse TB. Effects of angiotensin converting enzyme gene polymorphism on hypertension in Africa: A meta-analysis and systematic review. PloS one, 2019; 14(2): e0211054.

Zhu X, McKenzie CA, Forrester T, Nickerson DA, Broeckel U, Schunkert H, et al. Localization of a small genomic region associated with elevated ACE. American journal of human genetics.2000; 67(5): 1144–1153.

Liljedahl U, Karlsson J, Melhus H, Kurland L, Lindersson M, Kahan T, et al. A microarray minisequencing system for pharmacogenetic profiling of antihypertensive drug response. Pharmacogenetics. 2003; 13(1): 7-17.

Chung CM, Wang RY, Fann CS, Chen JW, Jong YS, Jou YS, et al. Fine-mapping angiotensin-converting enzyme gene: separate QTLs identified for hypertension and for ACE activity. PLoS One. 2013; 8(3): e56119.

Zhu X, Chang YP, Yan D, Weder A, Cooper R, Luke A, et al. Association between hypertension and genes in the rennin-angiotensin system. Hypertension. 2003; 41: 1027–1034.

Martı´nez-Rodrı´guez N, Posadas-Romero C, Villarreal-Molina T, Vallejo M, Del-Valle-Mondrago´n L, et al. Single Nucleotide Polymorphisms of the Angiotensin-Converting Enzyme (ACE) Gene Are Associated with Essential Hypertension and Increased ACE Enzyme Levels in Mexican Individuals. PLoS ONE. 2013; 8(5): e65700.


Download data is not yet available.


How to Cite
Osman, R. T., Hassan, D. A., Elamin, M. I., Elamin, M., Mursi, D., & Salih, M. A. M. (2022). Polymorphisms in Exon 13 of Angiotensin-Converting Enzyme Gene among Hypertensive Patients in Sudan. European Journal of Medical and Health Sciences, 4(2), 1–3. https://doi.org/10.24018/ejmed.2022.4.2.1211