2nd conference of Arab society of stem cell and molecular biology 7-9 February 2017,Cairo

1. Association of Angiotensin-converting Enzyme
Gene Insertion/ Deletion Polymorphism with
Increased Risk for Chronic Lymphocytic
Leukaemia
Dr. Ibrahim Khider
Al Neelain University-Sudan
2nd conference of Arab society of stem cell and molecular biology
7-9 February 2017,Cairo

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 Clonal B cell malignancy.
 Progressive accumulation of
long lived mature
lymphocytes.in the blood,
marrow, lymph nodes &
spleen.
CLL

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Angiotensin converting enzyme
(ACE)
 Angiotensin converting enzyme (ACE) converts
angiotensinogen-I to its physiologically active
peptide angiotensin-II.
 Angiotensin-II stimulates proliferation and
differentiation of hematopoietic stem cells through
angiotensin II type 1 receptors.

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Angiotensin Converting Enzyme
• Angiotensin converting enzyme (ACE) is a
dipeptidyl carboxy peptidase enzyme.
• It has two isoforms:
 A germinal form (gACE) that is only
found in male testis.
 A somatic form (sACE) found mainly in
the lungs, vascular endothelia and
kidneys and

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The kinin– kallikrein, and renin–angiotensin
systems (Sayed-Tabatabaei et al. 2006(

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ACE Gene

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The association between circulating ACE
levels and ACE gene polymorphisms
• Rigat et al showed a marked difference in ACE activity in
blood among the three genotypes:

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ACE Polymorphism and CLL
Population Association
between ACE
and HN
Reference
Turkey Positive Ibrahim AKALIN1 et al.
Sudanese (Unknown)

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ACE I/D polymorphism in
Sudanese
• Few studies were done concerning ACE I/D
polymorphism in Sudanese.
• Rania et al. studied AML population
 A significant association between the ACE I/D
polymorphism and AML.
• Lubna B et al. studied Ischemic Stroke
population:
 No significant association between the D-allele and
Ischemic Strokein the Sudanese population

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Aim of The Study
• Determine the frequency of ACE
genotypes in CLL patients and age-
matched controls.
• Investigate a possible association between
ACE I/D polymorphism and CLL.

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Methodology

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Materials and Methods
40CLL
Patients
40age-matched
controls
Sample

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Primers Sequence of ACE I/D
Polymorphism•
Primerdirection PrimerSequence
Forward :5'-CTGGAGACCACTCCCATCCTTTCT-3'
Reverse 5'-GATGTGGCCATCACATTCGTCAGAT-3'
Internal 5'-TGGGATTACAGGCGTGATACAG-3'

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PCR conditions
- Initial denaturation at 94°C for 3 minutes.
-Denaturation at 94°C for 1 minute
- Annealing at 52°C for 1 minute
- Extension at 72°C for 1 minute
- Final extension at 72°C for 10 minutes
30
cycles

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Gel Electrophoresis:

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PCR for ACE genotypes
1234
490bp
190bp
II ID DD

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Methodology
ResultsResults

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Distribution of ACE genotypes in
CLL patients and controls.
Control CLL
N(%) N(%)
OR (95% CI)
P-value
Genotype DD
32(80%) 8(20%)
6.3 (1.98,
2.04)
0.001
II
0 17(42.5%)
ID
8 (20%) 15(37.5%)

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Conclusion
 There is an association between ACE I/D
polymorphism and CLL.
There was no other study investigating this
association in Sudanese patients before,
however, several studies in other populations
(TURKEY) was consistent with our findings.

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+ In Future …..
 Assaying the ACE activity that will strengthen
our study.
 Recruiting a larger cohort of patients from
different sectors in Sudan is required to
highlight on the association between ACE I/D
polymorphism and hamatological
malignancies.

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