Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients

Amal Ahmed Mohamed; Dina M Abo-Elmatty; Alaa S Wahba; Omnia Ezzat Esmail; Hadeer Saied Mahmoud Salim; Wafaa Salah Mohammed Hegab; Mona Mostafa Farid Ghanem; Nadia Youssef Riad; Doaa Ghaith; Lamiaa I Daker; Shorouk Issa; Noha Hassan Radwan; Eman Sultan; Omar Mohamoud Azzam; Ehab A M El-Shoura

doi:10.1080/13813455.2023.2265078

Leptin Rs7799039 polymorphism is associated with type 2 diabetes mellitus Egyptian patients

Arch Physiol Biochem. 2023 Oct 15:1-13. doi: 10.1080/13813455.2023.2265078. Online ahead of print.

Authors

Amal Ahmed Mohamed¹, Dina M Abo-Elmatty², Alaa S Wahba², Omnia Ezzat Esmail³, Hadeer Saied Mahmoud Salim³, Wafaa Salah Mohammed Hegab⁴, Mona Mostafa Farid Ghanem⁵, Nadia Youssef Riad⁶, Doaa Ghaith⁷, Lamiaa I Daker⁸, Shorouk Issa⁹, Noha Hassan Radwan¹⁰, Eman Sultan¹¹, Omar Mohamoud Azzam¹², Ehab A M El-Shoura¹³

Affiliations

¹ Department of Biochemistry, National Hepatology and Molecular Biology & Tropical Medicine Research Institute, Cairo, Egypt.
² Department of Biochemistry, Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt.
³ Department of Biochemistry, Faculty of Pharmacy, Egyptian Russian University, Badr, Egypt.
⁴ Department of Internal Medicine, National Institute of Diabetes and Endocrinology, Cairo, Egypt.
⁵ Internal Medicine Department, National Research Centre, Cairo, Egypt.
⁶ Department of Clinical Pathology, National Heart Institute, Cairo, Egypt.
⁷ Department of Clinical Pathology, Kasr Alainy, Faculty of Medicine, Cairo University, Cairo, Egypt.
⁸ Department of Neurology, Faculty of Medicine, Fayoum University, Fayoum, Egypt.
⁹ Department of Endocrinology and Metabolism, Faculty of Medicine, Al-Azhar University, Cairo, Egypt.
¹⁰ Department of Clinical and Chemical Pathology, National Cancer Institute, Cairo, Egypt.
¹¹ Department of Endocrinology, The National Nutrition Institute, Cairo, Egypt.
¹² Department of Internal Medicine, Ahmed Maher Teaching Hospital, Cairo, Egypt.
¹³ Department of Clinical Pharmacy, Al-Azhar University, Assiut, Egypt.

PMID: 37840222
DOI: 10.1080/13813455.2023.2265078

Abstract

Background: Leptin (LEP) is an anti-obesity hormone that regulates food intake, energy expenditure, and glucose metabolism. The genetic variants in LEP and the LEP receptor (LEPR) gene may play an important role in the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. The current study aimed to investigate the association of serum LEP levels, and LEP polymorphisms in LEP (rs7799039, 2548 G/A) with T2DM in Egyptian patients.

Methods: A total of 205 subjects were included in the present case-control study, consisting of 100 T2DM patients and 105 healthy controls. The anthropometric, psychometric, and biochemical measurements were taken from all the subjects. The genotyping of LEP gene variants was carried out by polymerase chain reaction TaqMan technology. Serum LEP levels were measured by the ELISA technique.

Results: T2DM patients had significantly elevated levels of glycated haemoglobin (HbA1c), fasting blood sugar (FBS), postprandial blood sugar (PPBS), international normalisation ratio (INR), creatinine, urea, cholesterol, triglyceride (TG), and low-density lipoproteins (LDL) and significantly decreased high-density lipoprotein (HDL) compared to healthy subjects. serum LEP levels were significantly decreased p (<0.001) as compared to the control group. LEP gene SNP rs7799039 was associated with an increased diabetic risk with A allele being more frequent in T2DM patients than control subjects. The distribution of the AA genotype and GA genotype of LEP SNP rs7799039 was higher in the diabetic group than control one. In addition, AA + GA genotype carriers had significantly elevated HbA1c, FBS, PPBS, TG, and LDL levels and on the contrary, decreased serum LEP levels compared to GG homozygotes.

Conclusion: The genetic polymorphism rs7799039 showed a highly significant correlation with blood LEP. The co-dominant and dominant models of the LEP genetic polymorphism (rs7799039, 2548 G/A) were shown to have a significant correlation with complicated and uncomplicated diabetes individuals, but we have found that serum LEP levels were inversely related with control and diabetes patients. A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548 G/A) and serum LEP in patients and controls. LEP levels and its rs7799039 genetic variant may play a vital role in increasing T2DM susceptibility.

Keywords: Leptin; Leptin genetic polymorphism; Obesity; Type 2 diabetes mellitus.

Plain language summary

The present study revealed a positive significant association between the leptin (LEP) genetic polymorphism rs7799039, fasting blood sugar, and post-prandial blood sugar.LEP levels might be utilised to predict T2DM. The AA genotype of LEP rs7799039, 2548G/A (co-dominant model) raises the risk of diabetes compared to the GA genotype, and the A alle is considered a risk factor OR = 1.66.A positive significant association was found between LEP genetic polymorphism (rs7799039, 2548G/A) and serum LEP in patients and controls.