Genomics of Cardiovascular and Metabolic Diseases

Genetic Variant of Vitamin D Receptor

Genetic Variant of Vitamin D Receptor Gene Polymorphism in Osteoporotic Postmenopausal Sudanese Women Screened by Dual Energy X-ray Absorptiometry (DEXA)


Zeinab Hatim Abass1*, Amar M. Ismail2, Kamil A. Braima3, Mahmood A.Abdulla Hassan4, Siham M. A. Bakhit5

1 Department of Clinical Chemistry, Faculty of Medical Laboratory Science, Karary University, Khartoum, Sudan. 2 Department of Biochemistry and Molecular Biology, Faculty of Science and Technology, Al-Neelain University, Khartoum, Sudan.3 Department of Parasitology, Faculty of Veterinary, Murdoch University, Perth, Australia. 4Department of Biomedical Science, University of Malaya, Kuala Lumpur, Malaysia. 5Vice Chancellor, Alzaiem Alazhari University, Khartoum, Sudan.



Aim: A study to evaluate the vitamin D receptor (VDR) gene polymorphisms and its association with bone density among osteoporotic postmenopausal women in Sudan is reported. Method: A cross-sectional study involving 121 postmenopausal women was conducted, and based on the DEXA results, the subjects were classified into three groups, osteoporotic,T-score(≥ -2.5), osteopenia,T-score(-1 to -2.5) and normal, T-score(≤ -1) as the control group. Cdx2 single nucleotide polymorphisms (SNPs) in VDR were measured using RT-PCR TaqMan. Result The VDR SNP Cdx2 (rs11568820) AA genotype was found to be associated with osteoporosis and bone mineral density (BMD) at both the total hip and lumbar spine (L1–L4) (P=0.038, AOR 2.26 and P=0.017, AOR 8.1) under the additive and recessive model, respectively. No associations were observed among the other genotype polymorphisms (BsmI, TaqI, ApaI and FokI), bone mineral density (BMD), osteopenia and osteoporosis risk. This study is the first report of these findings from Sudan, which focused on VDR polymorphisms and bone health in the Sudanese population. Conclusion: The data suggest that genetic polymorphism in VDR Cdx2 SNP (rs11568820) is related to a higher risk of osteoporosis in postmenopausal Sudanese women.





Sahar Gamil1,  Jeanette Erdmann2,3,4 ,  Ihab B Abdalrahman5 , Abdelrahim O. Mohamed1,6

¹Department of Biochemistry, Faculty of Medicine, University of Khartoum, P.O. Box: 102, Khartoum, Sudan.

2Institute for Cardiogenetics, University of Lübeck, 23562 Lübeck, Germany

3DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, 23562 Lübeck, Germany

4University Heart Center Luebeck, 23562 Lübeck, Germany

5Department of Medicine, Faculty of Medicine, University of Khartoum, P.O. Box: 102, Khartoum, Sudan

6Neelain Institute for Medical Research, Al-Neelain University, Khartoum, Sudan


Email adresses: Sahar Gamil (, Jeanette Erdmann (, Ihab B Abdalrahman (, Abdelrahim O. Mohamed ( ).

Corresponding author: Sahar Gamil




Nitric oxide is important for the functional integrity of the vascular endothelium and is produced in endothelial cells by the enzyme endothelial nitric oxide synthase (eNOS). Essential Hypertension (EH)  has a strong genetic component, and the NOS3 gene, which encodes eNOS, represents an interesting candidate for contribution to the phenotype. The most clinically relevant polymorphisms in the NOS3 gene are rs1799983 in exon 7 (encoding Glu298Asp), a variable number tandem repeat (VNTR) in intron 4, and rs2070744 (T-786C) in the promoter region.


This study aims to investigate the association between these three polymorphisms in the NOS3 gene and EH in Sudanese patients.


Hypertensive patients (n = 157) with established hypertension and controls (n = 85)  with blood pressure measurements < 140/90, were included in this case control study. Genotypes at the NOS3 variants were determined using TaqMan and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) analyses. Genotype and allele frequencies were compared between the two groups by χ² analysis, and differences were expressed as odds ratios with 95% confidence intervals (CIs). P values < 0.05 were considered statistically significant.


The CC genotype of the rs2070744 polymorphism in NOS3 was found to be of higher frequency in patients compared with the controls (6.6% vs 6.1%, p= 0.02). Considering a dominant inheritance model, the frequency of TC+CC genotypes in patients was significantly higher than that in the control subjects (52.6% vs 34.1%, respectively; p< 0.01), with an odds ratio (95% CI) of 2.14 (1.23–3.74). In addition, the C allele was more frequent in the patients than the control group (29.6% vs 20%, p=0.03, OR= 1.84 (1.15-2.93)).


The results of this study indicated that the rs2070744 polymorphism in NOS3 may be a genetic susceptibility factor for EH in the Sudanese population.




Hypertrophic cardiomyopathy (HCM)


Background: Hypertrophic cardiomyopathy (HCM) is a myocardial disease characterized by an unexplained left ventricular hypertrophy (LVH), usually asymmetrical and involving the interventricular septum. HCM is a relatively frequent disorder, affecting one of 500 individuals from the general population. Some patients may not have any symptoms during their whole life, whereas in other cases, HCM may lead to severe symptoms such as syncope or dyspnea, sudden death, or congestive heart failure. It remains the most prevalent cause of inexplained sudden death in athletes during exercise. HCM is a familial disease in at least 50% of cases, with mainly an autosomal dominant mode of inheritance with variable expression and incomplete penetrance. It may be also inherited in autosomal recessive pattern or X-linked manner.  HCM are caused by mutations in nearly 22 different genes, more than 17 genes are involved in autosomal dominant HCM. The most frequently mutations fall within myosin heavy chain 7 (MYH7) and myosin binding protein C (MYBPC3), both accounting for up to 50% of HCM cases.

Case presentation: The present study reports the molecular results of a series of six unrelated Moroccan patients with HCM using for the first time in Morocco a next generation sequencing (NGS) customized multigene panel to investigate the two major HCM genes MYH7 and MYBPC3. Genetic testing lead to the identification of a novel MYBPC mutation (c.1049delA; p.Lys350fs) and three others previously described variants at heterozygous state.

Conclusion: Molecular diagnosis by NGS customized multigenes panel allowed us to set up a fast and firstline upon request cost-efficient strategy in order to screen various genes and diseases including HCM. This approach is well suited to general medical genetics laboratories dealing with almost all types of rare genetic diseases with  limited funds for a molecular testing more cost-effective.


Keywords: Hypertrophic cardiomyopathy, Moroccan patients, next-generation sequencing, customized panel.



obesity in Sudanese children

Association of a common rs9939609 variant in the fat mass and obesity-associated (FTO) gene with obesity in Sudanese children

1 Alyaa Awad 1, Azza Ahmed, Faisal M. Fadlelmola 1

1 Centre for Bioinformatics & Systems Biology (CBSB), Faculty of Science, University of




Background: Obesity disease develops as a result of interactions between the individual’s genetic component and his exposure to environmental risk factors such as lifestyle and food habits. It is well known that the Fat mass and obesity associated gene (FTO) is responsible of the body mass index (BMI) and the risk of obesity.  Aims: The study objective was to assess the association of FTO gene rs9939609 polymorphism with BMI in a sample of Sudanese children.

Methods: Twenty-seven subjects with ages ranging between 7-14 years were sampled from different locations of Khartoum State during the period of January to March 2016. Anthropometric measurements were taken from the subjects and then they were categorized into cases and controls based on their age, gender and BMI. Buccal swab samples were collected and the genomic DNA was extracted using guanidine chloride extraction method. PCR was performed using FTO rs9939609 forward and reverse primers. PCR-RFLP was performed using the Sca1 restriction enzyme.

Results: Out of twenty-seven samples, eleven participants show the homozygous wild type TT genotype with 41%, five participants show heterozygous TA genotype with 18% and eleven participants show homozygous mutant AA genotype with 41%. The results showed that the polymorphic A allele had the highest risk of obesity with p-value <0.0001.

 Conclusions: The study showed that there is a strong association between FTO rs9939609 and the risk of obesity among the studied sample of Sudanese children in Khartoum State. Further studies are required to confirm these findings.


Layla Ali poster

Layla Mohamed Ali Abdalla & Ghada Hassan Hag Ali
ABSTRACT Background: renal stone is increasingly serious issue in many parts of the world including Sudan. The vitamin D receptor (VDR) gene is a candidate gene for susceptibility to several diseases including renal stone. Aim: study was conducted to evaluate genetic polymorphism of VDR Fok1 in Sudanese patients with renal stone.
Methods: A case control study was conducted on 40 patients with renal stone and 40 healthy controls, blood samples were collected for DNA extraction. Demographic data and other data regarding life style and family history were obtained using pre-designed questionnaire. Genomic DNA was extracted from blood by guanidine chloride method. SNP of Vitamin D Receptor (VDR) Fok1 gene were analyzed using (PCR) and (RFLP). Statistical analysis was done using SPSS. Genotype distribution and allelic frequencies were compared between patients and controls.
Results: showed that the most affected age group was (51-60) year. The highest incidence of patients groups was among males – females, the most affected ethnic groups are Afro Asiatic (65%), most stones localized in kidneys (82.5%), the highest incidence of patients group regarding to BMI was normal weight (42.5%) , main diet type among patients was meat (47.5%), main source of water among patients was wells source (67%), (50%) of patients had urinary tract infection, the incidence of recurrent was (50%),and among patients (72.5%) had family history.
For molecular analysis result of RFLP digestion for both patient and control showed presence of polymorphism which was detected using (FokI) restriction enzyme. The wild type homozygote (FF) showed one band (265 base pair bp); heterozygote (Ff) three bands (265, 196 and 69 bp) and mutant homozygote (ff) two bands (196 and 69 bp). Most common genotype for renal stone patients is Ff representing (60%); the most common genotype for controls subjects was FF representing (82.5%). Conclusion: From this study the genotype frequencies of all genotypes of VDR Fok1 showed significant differences in genetics model between patients and controls (P = 0.000).
Presented by: Layla Mohamed Ali Abdalla, Teaching Assistance as a part-timer, Omdurman Islamic University.





*1Phillip, I. O. and 1Phillip, J. O


1Department of Genetics and Biotechnology, University of Calabar, PMB 1115, Calabar, Nigeria

*Author for correspondence: ; +2348067880200

Aim: To evaluate the endogenous expression of MIR-202 in an hepatic cell line and its corresponding effects on trib-1 level under conditions of metabolic and inflammatory stress.

Background: The Cardiovascular disease burden is a global one which accounts for high rate of mortality and morbidity in both developed and developing countries and as such, the development of new therapeutics targeting its onset is unending. Research from genome wide association studies (GWAS) has implicated human polymorphisms of the trib-1 gene to be associated with increased risk factors for cardiovascular diseases (CVD). MicroRNA studies have shown that trib-1 transcript is a target for MIR-202 and as such could have an effect on its protein stability.

Methods: HepG2 cells were cultured under in vitro conditions of high glucose and cytokine stimulation with interleukin-1 under concentrations of varying time intervals of 24hrs & 48hrs, after which the cells were harvested and mRNA of trib-1 and MIR-202 extracted using the spin-colum-based centrifugation, reversed transcribed and analysed for endogenous expressions of both trib-1 and MIR-202 using qPCR.

Result: it was observed that there was a significant (p < 0.05) decrease in trib-1 levels under these treatments of high glucose, stimulation with interleukin-1 and also a combination of both treatments whilst there was a consistent pattern of upregulation of MIR-202 in this conditions.

Conclusion: These suggests a possible interaction between trib-1 and MIR-202 which could affect trib-1 stability and also the potentials for MIR-202 to be involved in some cellular activities in HepG2 cells relating to this conditions and is in agreement with previous research findings which reveals the instability of trib-1 in lipid metabolism and could serve as a unique biomarker for such conditions and metabolic activities taking place in the liver.

Mrs Iquo Oyohosuho Phillip

Department of Genetics & Biotechnology

Faculty of Biological Science

University of Calabar,

Calabar, Nigeria.


Hala Abdalazeem


Hala A. Abdalbasit 1, Taiseer M. Ibrahim 2, Eman M. Yousif 3, Amear M. Dafallah4 , Hisham N. Altyeb5, Adam D. Abakar6

1Department of Clinical Chemistry, Faculty of Medical Laboratory Science University of Gezira Wadmedani, Sudan (presenter)

2Faculty of Medical Laboratory Science, Omdurman Islamic University, Khartoum, Sudan

3Faculty of Medical Laboratory Science, University of Gezira, Wadmedani, Sudan

4National Cancer Institute, University of Gezira, Wadmedani, Sudan

5Department of Microbiology, Faculty of Medical Laboratory Sciences, Sudan University of Science and Technology, Khartoum, Sudan

6Deanship of scientific research University of Gezira, Wadmedani, Sudan


This case control study aimed to assess the association of the FTO SNPs rs9939609, rs17817449 and rs1421085 with dietary intake, eating behavior and physical activity and secondly to determine the effect of the interaction between these FTO polymorphisms and the mentioned variables on BMI in the Sudanese adults. A cluster of single nucleotide polymorphisms in intron one of FTO gene have been associated with body mass index (BMI) and obesity. Sixty obese Sudanese adults were participated, BMI was calculated and structured questionnaire was used to asses food intake, eating behavior and physical activities. Guanidine Chloride method was used for DNA extraction, then PCR was carried to amplify FTO SNPs rs9939609, rs17817449 and rs1421085 region, normal sequencing was used to detect the SNP and the sequence was analyzed using Finsh T.V and Bio Edit programs. The presence of FTO rs9939609 and rs17817449 polymorphisms was detected and there was no rs1421085 within FTO gene in Sudanese obese adults. Another new polymorphism FTO rs9926289 and rs8046757 was detected when analyzing FTO rs9939609 and rs17817449 respectively. Novel FTO8063946 was found in one case which needs further study to detect it is effect. When comparing BMI and the main diet, there was significant statistical association (p. value =0.02) while with physical activity there was no association (p value =0.08).The sample size restricted statistical power of analyses, so further studies should be done to confirm the reliability.