The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

Faisal M Alzahrani; Jinan A Alhassan; Abdullah M Alshehri; Faraz A Farooqi; Maryam A Aldossary; Magdy K Abdelghany; Hafiz Ibrahim; Omar S El-Masry

doi:10.1016/j.sjbs.2023.103579

The impact of SELP gene Thr715Pro polymorphism on sP-selectin level and association with cardiovascular disease in Saudi diabetic patients: A cross-sectional case-control study

Saudi J Biol Sci. 2023 Mar;30(3):103579. doi: 10.1016/j.sjbs.2023.103579. Epub 2023 Feb 2.

Authors

Faisal M Alzahrani¹, Jinan A Alhassan¹, Abdullah M Alshehri², Faraz A Farooqi³, Maryam A Aldossary¹, Magdy K Abdelghany¹, Hafiz Ibrahim¹, Omar S El-Masry¹

Affiliations

¹ Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Imam Abdulrahman Bin Faisal University. P.O.Box 1982, Dammam 31441, Saudi Arabia.
² Department of Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, P.O.Box 1982, Dammam 31441, Saudi Arabia.
³ College of dentistry, Imam Abdulrahman Bin Faisal University, P.O.Box 1982, Dammam 31441, Saudi Arabia.

Abstract

Background: Cardiovascular diseases (CVD) are leading cause of mortality in patients with type 2 diabetes mellitus (T2DM). Increased soluble sP-selectin and 715Thr > Pro polymorphism were studied in CVD and T2DM, but association between them hasn't been explored in Saudi Arabia. We aimed to assess sP-selectin levels in T2DM and T2DM-associated CVD patients in comparison to healthy control cohort. Also, we sought to investigate relationship between Thr715Pro polymorphism and sP-selectin levels and disease state.

Methods: This is a cross-sectional case-control study. sP-selectin level (measured by Enzyme-linked immunosorbent assay) and prevalence of Thr715Pro polymorphism (assessed by Sanger sequencing) were investigated in 136 Saudi participants. The study comprised 3 groups: group1 included 41 T2DM patients; group 2 (48 T2DM patients with CVD), and group 3 (47 healthy controls).

Results: sP-selectin levels were significantly higher in diabetics and diabetics + CVD groups as compared to the corresponding control. In addition, results showed that the prevalence of 715Thr > Pro polymorphism is 11.75 % in the study population amongst the three study groups (9.55 % Thr/Pro, and 2.2 % Pro/Pro). No statistical difference was found between sP-selectin levels in subject carrying the wildtype genotype of this polymorphism and these who carry the mutant gene. There could be an association between this polymorphism and T2DM, whilst the polymorphism may protect diabetic patients from having CVD. However, odds ratio is not statistically significant in both cases.

Conclusion: Our study supports the previous researches' results that Thr715Pro is neither influencing the sP-selectin level nor the risk of CVD in T2DM patients.

Keywords: ACE-I, Angiotensin-converting enzyme inhibitors; ARB, Angiotensin II receptor blockers; BMI, Body-mass index; CAM, Cell adhesion molecule; CCB, Calcium channel blockers; CVD, Cardiovascular disease; Cardiovascular disease; DM, Diabetes mellitus; ELISA, Enzyme-linked immunosorbent assay; Gp1bα, Platelet glycoprotein 1b-alpha; IDF, International Diabetes Federation; IR, Insulin resistance; PMN, Polymorphonuclear leukocytes; PSGL-1, P-selectin glycoprotein ligand-1; SELP, P-selectin gene; T2DM, Type 2 diabetes mellitus; Thr715Pro polymorphism; Type 2 diabetes; WPb, Weibel-Palade Bodies; pP-selectin, Platelet P-selectin; sP-selectin; sP-selectin, Soluble P-selectin; vWF, Von-Willebrand factor.