Abstract
Insertion/deletion (I/D) polymorphism, of a 287-bp Alu repetitive sequence in intron 16 of the angiotensin-converting enzyme (ACE) gene has been shown to be associated with different types of diseases and has been widely investigated in different populations with different ethnic origins. Various reports were published suggesting inter-ethnic variations in the frequency of allelic forms of the ACE gene. The goal of this study was to test the distribution of alleles and the different genotypes of ACE (I/D) polymorphism in Bahraini subjects and compare the results with those obtained from other population studies. The Bahraini population is an Arabic peninsula population with a high prevalence of T2DM and hypertension. A total of 560 unrelated Bahraini individuals were recruited in this study and the presence (insertion)/absence (deletion) (I/D) polymorphism of a 287-bp Alu1 element inside intron 16 of the ACE gene was done by PCR-based assays and the presence or absence of the genotypes were analyzed by the gel electrophoresis. The distribution of II, ID, and DD genotypes showed differences among Bahraini subjects, and the frequency of the D allele was significantly (P < 0.05) higher in the studied group. The results obtained for the D allele are consistent with those obtained from previous studies among Arabs, Africans, and Caucasians, but differs significantly (P < 0.05) from those in Japanese and Chinese, thus proving the ethnic variation in the distribution of the ACE alleles in different populations.
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References
Ehlers MR, Riordan JF (1989) Angiotensin-converting enzyme: new concepts concerning its biological role. Biochemistry 28(13):5311–5318
Wang JG, Staessen JA (2000) Genetic polymorphisms in the renin-angiotensin system: relevance for susceptibility to cardiovascular disease. Eur J Pharmacol 410:289–302
Skidgel RA, Erdös EG (1993) Biochemistry of angiotensin converting enzyme. In: Robertson JIS, Nicholls MG (eds) The renin-angiotensin system, vol 1. Gower Medical Publishers, London, pp 10.10–10.11
Rigat B, Hubert C, Alhenc-Gelas F, Corvol P, Soubrier F (1990) An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene account for half the variance of serum enzyme levels. J Clin Invest 86:1343–1346
Tiret L, Rigat B, Visvikis S, Breda C, Corvol P, Cambien F, Soubrier F (1992) Evidence, from combined segregation and linkage analysis, that a variant of the angiotensin I-converting enzyme (ACE) gene controls plasma ACE levels. Am J Hum Genet 51(1):197–205
Kennon B, Petrie JR, Small M, Connell JM (1999) Angiotensin-converting enzyme gene and diabetes mellitus. Diabet Med 16(6):448–458
Ramachandran V, Ismail P, Stanslas J, Shamsudin N, Moin S, Jas M (2008) Association of insertion/deletion polymorphism of angiotensin-converting enzyme gene with essential hypertension and type 2 diabetes mellitus in Malaysian subjects. J Renin Angiotensin Aldosterone Syst 9(4):208–214
Baroudi T, Bouhaha R, Moran-Moguel C, Sanchez-Corona J, Ben Maiz H, KammounAbid H, Benammar-Elgaaied A (2009) Association of the insertion/deletion polymorphism of the angiotensin-converting enzyme gene with type 2 diabetes in two ethnic groups of Jerba Island in Tunisia. J Renin Angiotensin Aldosterone Syst 10(1):35–40
Fava S, Azzopardi J, Ellard S, Hattersley AT (2001) ACE gene polymorphism as a prognostic indicator in patients with type 2 diabetes and established renal disease. Diabetes Care 24:2115–2120
ArzuErgen H, Hatemi H, Agachan B, Camlica H, Isbir T (2004) Angiotensin-I converting enzyme gene polymorphism in Turkish type 2 diabetic patients. Exp Mol Med 36(4):345–350
Palomo-Piñón S, Gutiérrez-Rodríguez ME, Díaz-Flores M, Sánchez-Barrera R, Valladares-Salgado A, Utrera-Barillas D, Durán-Reyes G, Galván-Duarte RE, Trinidad-Ramos P, Cruz M (2009) DD genotype of angiotensin-converting enzyme in type 2 diabetes mellitus with renal disease in Mexican Mestizos. Nephrology (Carlton) 14(2):235–239
Sobti RC, Maithil N, Thakur H, Sharma Y, Talwar KK (2010) Association of ACE and FACTOR VII gene variability with the risk of coronary heart disease in north Indian population. Mol Cell Biochem 341(1–2):87–98
Thameem F, Voruganti VS, He X, Nath SD, Blangero J, MacCluer JW, Comuzzie AG, Abboud HE, Arar NH (2008) Genetic variants in the renin-angiotensin system genes are associated with cardiovascular-renal-related risk factors in Mexican Americans. Hum Genet 124(5):557–559
Bawazier LA, Sja’bani M, Haryana SM, Soesatyo MH, Sadewa AH (2010) Relationship of angiotensin converting enzyme gene polymorphism and hypertension in Yogyakarta, Indonesia. Acta Med Indones 42(4):192–198
Rigat B, Hubert C, Corvol P, Soubrier F (1999) PCR detection of the insertion/deletion polymorphism of the human angiotensin converting enzyme gene (DCP1) (dipeptidylcarboxypeptidase 1). Nucleic Acids Res 20(6):1433
Thomas GN, Tomlinson B, Chan JC, Sanderson JE, Cockram CS, Critchley JA (2001) Renin-angiotensin system gene polymorphisms, blood pressure, dyslipidemia, and diabetes in Hong Kong Chinese: a significant association of the ACE insertion/deletion polymorphism with type 2 diabetes. Diabetes Care 24(2):356–361
Jeunemaitre X, Lifton RP, Hunt SC, Williams RR, Lalouel JM (1992) Absence of linkage between the angiotensin converting enzyme locus and human essential hypertension. Nat Genet 1:72–75
Marre M, Bernadet P, Gallois F, Savagner Y, Guyene TT, Hallab M, Cambien F, Passa P, Alhenc-Gelas F (1994) Relationships between angiotensin I converting enzyme gene polymorphism, plasma levels, and diabetic retinal and renal complications. Diabetes 43(3):384–388
Staessen JA, Wang JG, Ginocchio V, Petrov G, Saavedra AP, Soubrier F, Vlietinck R, Fagard R (1997) The deletion/insertion polymorphism of the angiotensin converting enzyme gene and cardiovascular-renal risk. J Hypertens 15(12, Pt 2):1579–1592
Kunz R, Bork JP, Fritsche L, Ringel J, Sharma AM (1998) Association between the angiotensin-converting enzyme-insertion/deletion polymorphism and diabetic nephropathy: a methodologic appraisal and systematic review. J Am Soc Nephrol 9(9):1653–1663
Taal MW (2000) Angiotensin-converting enzyme gene polymorphisms in renal disease: clinically relevant? Curr Opin Nephrol Hypertens 9(6):651–657
Thomas GN, Young RP, Tomlinson B, Woo KS, Sanderson JE, Critchley JA (2000) Renin-angiotensin-aldosterone system gene polymorphisms and hypertension in Hong Kong Chinese. Clin Exp Hypertens 22(1):87–97
Grimm R, Rettig R (2002) Association studies between the angiotensin-converting enzyme insertion/deletion polymorphism and hypertension: still interesting? J Hypertens 20(6):1049–1051
Tascilar N, Dursun A, Ankarali H, Mungan G, Ekem S, Baris S (2009) Angiotensin-converting enzyme insertion/deletion polymorphism has no effect on the risk of atherosclerotic stroke or hypertension. J Neurol Sci 285(1–2):137–141
Barley J, Blackwood A, Carter ND, Crews DE, Cruickshank JK, Jeffery S, Ogunlesi AO, Sagnella GA (1994) Angiotensin converting enzyme insertion/deletion polymorphism: association with ethnic origin. J Hypertens 12(8):955–957
Altshuler D, Kruglyak L, Lander E (1998) Genetic polymorphisms and disease. N Engl J Med 338(22):1626
Pasha MA, Khan AP, Kumar R, Ram RB, Grover SK, Srivastava KK, Selvamurthy W, Brahmachari SK (2002) Variations in angiotensin-converting enzyme gene insertion/deletion polymorphism in Indian populations of different ethnic origins. J Biosci 27(1 Suppl 1):67–70
Al-Mahroos F, McKeigue PM (1998) High prevalence of diabetes in Bahrainis. Association with ethnicity and raised plasma cholesterol. Diabetes Care 21:936–942
Al-Mahroos F, Al-Roomi K, Mckeigue PM (2000) Relation of high blood pressure to glucose intolerance, plasma lipids and educational status in an Arabian Gulf population. Int J Epidemiol 29:71–76
Shanmugan V, Sell KW, Saha BK (1993) Mistyping ACE heterozygotes. PCR Methods Appl 3(2):120–121
Lindpaintner K, Pfeffer MA, Kreutz R, Stampfer MJ, Grodstein F, LaMotte F, Buring J, Hennekens CH (1995) A prospective evaluation of an angiotensin-converting-enzyme gene polymorphism and the risk of ischemic heart disease. N Engl J Med 332(11):706–711
World Health Organisation (1999) Definition, diagnosis and classification of diabetes mellitus and its complications; Report of a WHO Consultation. Part 1: Diagnosis and classification of diabetes mellitus. Geneva, Switzerland
Al-Hinai AT, Hassan MO, Simsek M, Al-Barwani H, Bayoumi R (2002) Genotypes and allele frequencies of angiotensin converting enzyme (ACE) insertion/deletion polymorphism among Omanis. SQU J Sci Res: Med Sci 4(1–2):25–27
Bayoumi R, Simsek M, Yahya TM, Bendict S, Al-Hinai A, Al-Barwani H, Hassan MO (2006) Insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene among Sudanese, Somalis, Emiratis, and Omanis. Hum Biol 78(1):103–108
Frossard PM, Obineche EN, Elshahat YI, Lestringant GG (1997) Deletion polymorphism in the angiotensin-converting enzyme gene is not associated with hypertension in a Gulf Arab population. Clin Genet 51(3):211–213
Comas D, Calafell F, Benchemsi N, Helal A, Lefranc G, Stoneking M, Batzer MA, Bertranpetit J, Sajantila A (2000) Alu insertion polymorphisms in NW Africa and the Iberian Peninsula: evidence for a strong genetic boundary through the Gibraltar Straits. Hum Genet 107:312–319
Salem AH, Batzer MA (2009) High frequency of the D allele of the angiotensin-converting enzyme gene in Arabic populations. BMC Res Notes 8(2):99–104
Rutledge DR, Browe CS, Ross EA (1994) Frequencies of the angiotensinogen gene and angiotensin I converting enzyme (ACE) gene polymorphisms in African Americans. Biochem Mol Biol Int 34(6):1271–1275
Cambien F, Poirier O, Lecerf L, Evans A, Cambou JP, Arveiler D, Luc G, Bard JM, Bara L, Ricard S et al (1992) Deletion polymorphism in the gene for angiotensin-converting enzyme is a potent risk factor for myocardial infarction. Nature 359(6396):641–644
Raynolds MV, Bristow MR, Bush EW, Abraham WT, Lowes BD, Zisman LS, Taft CS, Perryman MB (1993) Angiotensin-converting enzyme DD genotype in patients with ischaemic or idiopathic dilated cardiomyopathy. Lancet 342:1073–1075
Nomura H, Koni I, MichishitaY Morise T, Takeda R (1994) Angiotensin-converting enzyme gene polymorphism in haemodialysis patients. Lancet 343(8895):482–483
Doi Y, Yoshizumi H, Yoshinari M, Iino K, Yamamoto M, Ichikawa K, Iwase M, Fujishima M (1996) Association between a polymorphism in the angiotensin-converting-enzyme gene and microvascular complications in Japanese patients with NIDDM. Diabetologia 39(1):97–102
Kario K, Kanai N, Nishiuma S, Fujii T, Saito K, Matsuo T, Matsuo M, Shimada K (1997) Hypertensive nephropathy and the gene for angiotensin-converting enzyme. Arterioscler Thromb Vasc Biol 17(2):252–256
Lee EJ (1994) Population genetics of the angiotensin-converting enzyme in Chinese. Br J Clin Pharmacol 37(2):212–214
Evans AE, Poirier O, Kee F, Lecerf L, McCrum E, Falconer T, Crane J, O’Rourke DF, Cambien F (1994) Polymorphisms of the angiotensin-converting-enzyme gene in subjects who die from coronary heart disease. Q J Med 87(4):211–214
Pujia A, Gnasso A, Irace C, Dominijanni A, Zingone A, Perrotti N, Colonna A, Mattioli PL (1994) Association between ACE-D/D polymorphism and hypertension in type II diabetic subjects. J Hum Hypertens 8(9):687–691
Ruiz J, Blanche H, Cohen N, Velho G, Cambien F, Cohen D, Passa P, Froguel P (1994) Insertion/deletion polymorphism of the angiotensin-converting enzyme gene is strongly associated with coronary artery disease in non-insulin-dependent diabetes mellitus. Proc Natl Acad Sci USA 91(9):3662–3665
Acknowledgment
The authors gratefully acknowledge Colonel Dr. Abdulla Darweesh, Chairman of Department of Pathology in BDF hospital & Major Khalid Matar, Chief of Medical Technologists for giving the opportunity to collect blood samples, for the current study, from the BDF hospital.
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Al-Harbi, E.M., Farid, E.M., Gumaa, K.A. et al. Genotypes and allele frequencies of angiotensin-converting enzyme (ACE) insertion/deletion polymorphism among Bahraini population with type 2 diabetes mellitus and related diseases. Mol Cell Biochem 362, 219–223 (2012). https://doi.org/10.1007/s11010-011-1146-1
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DOI: https://doi.org/10.1007/s11010-011-1146-1