Association of VEGFA variants with altered VEGF secretion and type 2 diabetes: A case-control study

Nejla Sellami; Laila Ben Lamine; Amira Turki; Sameh Sarray; Mohammed Jailani; Abrar K Al-Ansari; Mohamed Ghorbel; Touhami Mahjoub; Wassim Y Almawi

doi:10.1016/j.cyto.2018.03.003

Association of VEGFA variants with altered VEGF secretion and type 2 diabetes: A case-control study

Cytokine. 2018 Jun:106:29-34. doi: 10.1016/j.cyto.2018.03.003. Epub 2018 Mar 10.

Authors

Nejla Sellami¹, Laila Ben Lamine², Amira Turki³, Sameh Sarray⁴, Mohammed Jailani⁵, Abrar K Al-Ansari⁵, Mohamed Ghorbel², Touhami Mahjoub², Wassim Y Almawi⁶

Affiliations

¹ Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia; Faculty of Science of Bizerte, University of Carthage, Tunisia.
² Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia.
³ Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), Faculty of Pharmacy of Monastir, University of Monastir, Tunisia; Department of Laboratory Medicine, Northern Border University, Ara'ar, Saudi Arabia.
⁴ Faculty of Sciences, El-Manar University, Tunis, Tunisia; College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
⁵ College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain.
⁶ Faculty of Sciences, El-Manar University, Tunis, Tunisia; School of Pharmacy, Lebanese American University, Byblos, Lebanon. Electronic address: wassim.almawi@lau.edu.lb.

PMID: 29533820
DOI: 10.1016/j.cyto.2018.03.003

Abstract

Background: Vascular endothelial growth factor (VEGF) contributes to type 2 diabetes (T2DM) pathogenesis, and genetic variations in VEGFA gene were suggested to influence VEGF secretion and T2DM pathogenesis.

Aim: To evaluate the association of specific VEGFA variants with altered VEGF levels, and with T2DM among Tunisians.

Subjects and methods: A retrospective case-control study, performed on 815 T2DM patients, and 805 healthy controls. VEGF levels were measured by ELISA, genotyping of VEGFA variants was done by allelic exclusion method (real-time PCR).

Results: MAF of rs1570360, rs2010963, rs25648, rs833068, rs3025036, and rs3025039 were significantly different between T2DM cases and controls. Increased T2DM risk was associated with rs699947, rs1570360, and rs3025020, while reduced T2DM risk was seen with rs1547651, rs2010963, rs25648, rs3025036, and rs3025039 genotypes, thus assigning T2DM susceptibility and protection, respectively. Reduced VEGF levels were associated with rs833061, rs2010963, and rs3025039 heterozygosity and rs3025036 major allele homozygosity in T2DM cases, while increased VEGF levels were seen in rs833070 homozygous major allele genotype. Both rs699947 and rs1570360 positively, while rs2010963 and rs3025036 negatively correlated with fasting glucose. In addition, rs699947 positively correlated with LDL-cholesterol, and rs3025039 positively correlated with diabetes duration, but negatively with HbA1c and serum triglycerides. Haploview analysis identified Block 1 containing 8 loci, and Block 2 with the remaining 3 loci. Haplotypes ACTGCCGG and AACGGCGA (Block 1) were negatively associated with T2DM, while haplotype CCC was positively and haplotype CGC (Block 2) were negatively associated with T2DM.

Conclusion: This study confirms the contribution of altered VEGF secretion, resulting from genetic variation in VEGFA gene into T2DM pathogenesis, hence supporting role for VEGFA as T2DM candidate locus.

Keywords: Genotype; Haplotypes; Type 2 diabetes; Vascular endothelial growth factor.

MeSH terms

Case-Control Studies
Diabetes Mellitus, Type 2 / blood
Diabetes Mellitus, Type 2 / genetics*
Female
Genetic Association Studies*
Genetic Predisposition to Disease*
Haplotypes / genetics
Humans
Linkage Disequilibrium / genetics
Male
Middle Aged
Polymorphism, Single Nucleotide / genetics*
Vascular Endothelial Growth Factor A / blood
Vascular Endothelial Growth Factor A / genetics*

Substances

Vascular Endothelial Growth Factor A