A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus

Background: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Met...

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Main Authors: Usha Adiga, Sachidananda Adiga, P.B. Nandit, Lakshmi Manjeera, Aparna Rao, Abdul-Kareem Mohammed Ghilan, Atif Abdulwahab A. Oyouni, Yousef M. Hawsawi, Abdulrahman Theyab, Mohammad Algahtani, Othman R. Alzahrani, Ravi Mundugaru
Format: Article
Language:English
Published: Elsevier 2022-01-01
Series:Journal of King Saud University: Science
Subjects:
Online Access:http://www.sciencedirect.com/science/article/pii/S1018364721003244
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author Usha Adiga
Sachidananda Adiga
P.B. Nandit
Lakshmi Manjeera
Aparna Rao
Abdul-Kareem Mohammed Ghilan
Atif Abdulwahab A. Oyouni
Yousef M. Hawsawi
Abdulrahman Theyab
Mohammad Algahtani
Othman R. Alzahrani
Ravi Mundugaru
author_facet Usha Adiga
Sachidananda Adiga
P.B. Nandit
Lakshmi Manjeera
Aparna Rao
Abdul-Kareem Mohammed Ghilan
Atif Abdulwahab A. Oyouni
Yousef M. Hawsawi
Abdulrahman Theyab
Mohammad Algahtani
Othman R. Alzahrani
Ravi Mundugaru
author_sort Usha Adiga
collection DOAJ
description Background: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Methods: Hundred GDM patients and an equal number of BMI and gestational age matched normal glucose tolerant pregnant women were recruited as cases and controls. Five milliliters of venous blood was drawn for biochemical and genetic analysis. Genotyping of LEPR (Gln223Arg) was performed by PCR-RFLP. Fasting blood sugar, leptin, insulin, C-peptide, and lipid profile estimations were done. Various insulin resistance models were constructed using suitable formulae. The statistical analysis was performed using SPSS 23.0 software. Results: There was no significant association found between LEPR gene polymorphism with leptin levels and insulin resistance in GDM. However, Odd’s ratio showed that individuals with the “A” allele were at 1.25 times higher risk of developing GDM. HOMA B-cell significantly varied among LEPR genotypes (p < 0.0001), values being double in AA genotype, compared to AG (p < 0.05), ten times higher in AA compared to GG (p < 0.0001). There was no significant deviation of the genotype frequency distributions for rs1137101 variants from HWE in GDM cases, suggesting that alleles were in equilibrium. Conclusion: The study established a cycle of gene polymorphism altering leptin levels which in turn can alter insulin secretion and insulin resistance, contributing to dyslipidemia of pregnancy as well as gestational diabetes.
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spelling doaj.art-520cf82597624d3c83bd43718fa462f52022-12-21T18:47:00ZengElsevierJournal of King Saud University: Science1018-36472022-01-01341101662A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitusUsha Adiga0Sachidananda Adiga1P.B. Nandit2Lakshmi Manjeera3Aparna Rao4Abdul-Kareem Mohammed Ghilan5Atif Abdulwahab A. Oyouni6Yousef M. Hawsawi7Abdulrahman Theyab8Mohammad Algahtani9Othman R. Alzahrani10Ravi Mundugaru11Department of Biochemistry, KS Hegde Medical Academy, Nitte-DU, India; Corresponding author.Department of Pharmacology, KS Hegde Medical Academy, Nitte-DU, IndiaDepartment of Pharmacology, KS Hegde Medical Academy, Nitte-DU, IndiaDepartment of Obstetrics and Gynecology, KS Hegde Medical Academy, Nitte-DU, IndiaDepartment of Obstetrics and Gynecology, KS Hegde Medical Academy, Nitte-DU, IndiaDepartment of Botany and Microbiology, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi ArabiaDepartment of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia; Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi ArabiaResearch Center, King Faisal Specialist Hospital and Research Center, MBC-J04, P.O. Box 40047, Jeddah 21499, Saudi ArabiaDepartment of Laboratory Medicine, Security Forces Hospital, Mecca, Saudi ArabiaDepartment of Laboratory Medicine, Security Forces Hospital, Mecca, Saudi ArabiaDepartment of Biology, Faculty of Sciences, University of Tabuk, Tabuk, Saudi Arabia; Genome and Biotechnology Unit, Faculty of Sciences, University of Tabuk, Tabuk, Saudi ArabiaDepartment of Pharmacology, DM Wayanad Institute of Medical Sciences, Wayanad, Kerala, IndiaBackground: The role of genetics in pathophysiology of gestational diabetes mellitus (GDM) is least explored. Objective of the study is to find the association of leptin receptor (LEPR) gene polymorphism with GDM and its role in altered leptin levels, insulin resistance, and dyslipidemia in GDM. Methods: Hundred GDM patients and an equal number of BMI and gestational age matched normal glucose tolerant pregnant women were recruited as cases and controls. Five milliliters of venous blood was drawn for biochemical and genetic analysis. Genotyping of LEPR (Gln223Arg) was performed by PCR-RFLP. Fasting blood sugar, leptin, insulin, C-peptide, and lipid profile estimations were done. Various insulin resistance models were constructed using suitable formulae. The statistical analysis was performed using SPSS 23.0 software. Results: There was no significant association found between LEPR gene polymorphism with leptin levels and insulin resistance in GDM. However, Odd’s ratio showed that individuals with the “A” allele were at 1.25 times higher risk of developing GDM. HOMA B-cell significantly varied among LEPR genotypes (p < 0.0001), values being double in AA genotype, compared to AG (p < 0.05), ten times higher in AA compared to GG (p < 0.0001). There was no significant deviation of the genotype frequency distributions for rs1137101 variants from HWE in GDM cases, suggesting that alleles were in equilibrium. Conclusion: The study established a cycle of gene polymorphism altering leptin levels which in turn can alter insulin secretion and insulin resistance, contributing to dyslipidemia of pregnancy as well as gestational diabetes.http://www.sciencedirect.com/science/article/pii/S1018364721003244Gestational diabetes mellitusInsulin resistanceHardy-weinberg equillibriumLeptin
spellingShingle Usha Adiga
Sachidananda Adiga
P.B. Nandit
Lakshmi Manjeera
Aparna Rao
Abdul-Kareem Mohammed Ghilan
Atif Abdulwahab A. Oyouni
Yousef M. Hawsawi
Abdulrahman Theyab
Mohammad Algahtani
Othman R. Alzahrani
Ravi Mundugaru
A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
Journal of King Saud University: Science
Gestational diabetes mellitus
Insulin resistance
Hardy-weinberg equillibrium
Leptin
title A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
title_full A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
title_fullStr A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
title_full_unstemmed A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
title_short A cross-sectional study on the association of single nucleotide polymorphism of leptin receptor (Gln223Arg) and insulin resistance in gestational diabetes mellitus
title_sort cross sectional study on the association of single nucleotide polymorphism of leptin receptor gln223arg and insulin resistance in gestational diabetes mellitus
topic Gestational diabetes mellitus
Insulin resistance
Hardy-weinberg equillibrium
Leptin
url http://www.sciencedirect.com/science/article/pii/S1018364721003244
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