Basic Study
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World J Diabetes. Jul 15, 2019; 10(7): 396-402
Published online Jul 15, 2019. doi: 10.4239/wjd.v10.i7.396
Epidermal growth factor receptor rs17337023 polymorphism in hypertensive gestational diabetic women: A pilot study
Russell S Martins, Taimur Ahmed, Sabah Farhat, Sana Shahid, Syeda Sadia Fatima
Russell S Martins, Taimur Ahmed, Medical College, Aga Khan University, Karachi, Sindh 74800, Pakistan
Sabah Farhat, Syeda Sadia Fatima, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Sindh 74800, Pakistan
Sana Shahid, Department of Physiology, Sir Syed Medical College for Girls, Karachi, Pakistan
Author contributions: Fatima SS and Shahid S designed research; Martins RS, Ahmed T and Farhat S performed research; Fatima SS and Shahid S contributed new reagents/analytic tools; Fatima SS analyzed data; and all authors wrote the paper and approved for publication.
Supported by Pakistan Health Research Counsel, No. 119/2016/RDC/AKU.
Institutional review board statement: The institutional ethics committee approved the research protocol, No. # 4523-BBS-ERC-16.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
ARRIVE guidelines statement: The manuscript abides the guidelines
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Syeda Sadia Fatima, MD, MPhil, PhD, Assistant Professor, Doctor, Dr, Department of Biological and Biomedical Sciences, Aga Khan University, Karachi, Sindh 74800, Pakistan. sadia.fatima@aku.edu
Telephone: +92-2134864564
Received: March 20, 2019
Peer-review started: March 22, 2019
First decision: May 31, 2019
Revised: June 10, 2019
Accepted: June 21, 2019
Article in press: June 21, 2019
Published online: July 15, 2019
Processing time: 118 Days and 3.9 Hours
Abstract
BACKGROUND

Women with gestational diabetes mellitus have an increased risk of developing gestational hypertension, which can increase fetal and neonatal morbidity and mortality. In the past decade, single nucleotide polymorphisms in several genes have been identified as risk factors for development of gestational hypertension. The epidermal growth factor receptor activates tyrosine kinase mediated blood vessels contractility; and inflammatory cascades. Abnormalities in these mechanism are known to contribute towards hypertension. It is thus plausible that polymorphisms in the epidermal growth factor receptor gene would be associated with the development of hypertension in women with gestational diabetes.

AIM

To determine whether the epidermal growth factor receptor rs17337023 SNP is associated with the occurrence of hypertension in gestational diabetic women.

METHODS

This pilot case-control study was conducted at two tertiary care hospitals in Karachi, from January 2017-August 2018. Two hundred and two women at 28 week of gestation with gestational diabetes were recruited and classified into normotensive (n = 80) and hypertensive (n = 122) groups. Their blood samples were genotyped for epidermal growth factor receptor polymorphism rs17337023 using tetra-ARMS polymerase chain reaction. Descriptive analysis was applied on baseline data. Polymorphism data was analyzed for genotype and allele frequency determination using chi-squared statistics. In all cases, a P value of < 0.05 was considered significant.

RESULTS

Subjects were age-matched and thus no difference was observed in relation to age of the study subjects (P >0.05). Body fat percentage was significantly higher in hypertensive females as compared to normotensive subjects (35.138 ± 4.29 Case vs 25.01 ± 8.28 Control; P < 0.05). Similarly, systolic and diastolic blood pressures among groups were significantly higher in hypertensive group than the normotensive group (P < 0.05). Overall epidermal growth factor receptor rs17337023 polymorphism genotype frequency was similar in both groups, with the heterozygous AT genotype (56 in Case vs 48 in Control; P = 0. 079) showing predominance in both groups. Furthermore, the odds ratio for A allele was 1.282 (P = 0.219) and for T allele was 0.780 (P = 0.221) in this study.

CONCLUSION

This pilot study indicates that polymorphisms in rs17337023 may not be involved in the pathophysiology of gestational hypertension in gestational diabetes via inflammatory cascade mechanism. Further large-scale studies should explore polymorphism in epidermal growth factor receptor and other genes in this regard.

Keywords: Gestational diabetes mellitus; Gestational hypertension; Epidermal growth factor receptor; rs17337023; Single nucleotide polymorphism; Polymorphism; Case-control

Core tip: Gestational Hypertension (GHTN) can increase risk of fetal and neonatal morbidity and mortality. Many environmental, nutritional and genetic factors are related to the development of GHTN. Among them, Epidermal Growth Factor Receptor (EGFR) has been found to contribute to arterial hypertension. It is thus plausible that Single nucleotide polymorphisms (SNPs) in EGFR gene would be associated with the development of GHTN in women with GDM. This pilot study indicated that EGFR rs17337023 polymorphism may not be involved in the pathophysiology of GHTN in GDM positive females in a local population. Further large-scale studies should explore SNPs in EGFR and other genes in this regard.