Endocrinology and Metabolism

Hayder A. Giha (Giha HA)

2 Articles

Clinical Study
Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population: Faris Elbahi Joatar, Ali Ahmed Al Qarni, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Nagalla Das, Khalid Gumaa, Hayder A. Giha; Endocrinol Metab. 2017;32(3):360-369. Published online September 18, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.3.360

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Background

Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of ‘which SNPs in which populations.’ The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.

Methods

Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.

Results

None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.

Conclusion

Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Citations

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International Journal of Molecular Sciences.2024; 25(10): 5059. CrossRef
Relationship between single nucleotide polymorphism studies in ghrelin gene with obesity subjects
May Salem Al-Nbaheen
Journal of King Saud University - Science.2023; 35(1): 102393. CrossRef
Leu72Met Polymorphism in Ghrelin Gene: A Potential Risk Factor for Hypertension in Type 2 Diabetes Patients
Monika Buraczynska, Jakub Golacki, Wojciech Zaluska
Diabetes, Metabolic Syndrome and Obesity.2023; Volume 16: 557. CrossRef
Асоціації варіантів гена GHRL із розвитком ожиріння та метаболічних порушень у дітей
A. Abaturov, A. Nikulina
CHILD`S HEALTH.2023; 18(4): 255. CrossRef
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Mai M. Madkour, Afaf M. El-Said, Abd El-Aziz A. El-Refaey, Abd El-Aziz F. Abd El-Aziz, Fardous F. El-Senduny
Egyptian Journal of Medical Human Genetics.2022;[Epub] CrossRef
Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes
Hayder A. Giha, Faris E. Joatar, Dhuha M. B. AlDehaini, Zainab H. A. Malalla, Muhalab E. Ali, Ali A. Al Qarni
Hormone Molecular Biology and Clinical Investigation.2022; 43(3): 297. CrossRef
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Mohammad Muzaffar Mir, Rashid Mir, Mushabab Ayed Abdullah Alghamdi, Javed Iqbal Wani, Zia Ul Sabah, Mohammed Jeelani, Vijaya Marakala, Shahzada Khalid Sohail, Mohamed O’haj, Muffarah Hamid Alharthi, Mohannad Mohammad S. Alamri
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Ethnicity-Specific Association Between Ghrelin Leu72Met Polymorphism and Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis
Rong Huang, Sai Tian, Rongrong Cai, Jie Sun, Yanjue Shen, Shaohua Wang
Frontiers in Genetics.2018;[Epub] CrossRef

Association of Plasma Ghrelin Levels with Insulin Resistance in Type 2 Diabetes Mellitus among Saudi Subjects: Ali Ahmed Al Qarni, Faris Elbahi Joatar, Nagalla Das, Mohamed Awad, Mona Eltayeb, Ahmed Gasim Al-Zubair, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Khalid Gumaa, Hayder A. Giha; Endocrinol Metab. 2017;32(2):230-240. Published online May 29, 2017; DOI: https://doi.org/10.3803/EnM.2017.32.2.230

5,628 View
54 Download
21 Web of Science
20 Crossref

Abstract PDF PubReader

Background

Although the exact mechanism of insulin resistance (IR) has not yet been established, IR is the hallmark characteristic of type 2 diabetes mellitus (T2DM). The aim of this study was to examine the relationship between plasma ghrelin levels and IR in Saudi subjects with T2DM.

Methods

Patients with T2DM (n=107, cases) and non-diabetic apparently healthy subjects (n=101, controls) from Saudi Arabia were included in this study. The biochemical profiles and plasma insulin levels of all subjects were analyzed, and IR was estimated using the homeostatic model assessment of insulin resistance (HOMA-IR) index. Active ghrelin levels in plasma were measured using the radioimmunoassay technique.

Results

Only 46.7% (50 of 107) of the T2DM subjects had IR, including 26% (28 of 107) with severe IR (HOMA-IR ≥5), while 5.9% (six of 101) of the controls had moderate IR (3 ≤HOMA-IR <5). HOMA-IR values were not associated with age, disease duration, or gender. Importantly, T2DM itself and the co-occurrence of IR with T2DM were significantly associated with low plasma ghrelin levels. However, ghrelin levels were inversely correlated with the HOMA-IR index, body weight, and fasting plasma insulin levels, mainly in the control subjects, which was indicative of the breakdown of metabolic homeostasis in T2DM.

Conclusion

The prevalence of IR was relatively low, and IR may be inversely associated with plasma ghrelin levels among Saudi patients with T2DM.

Citations

Citations to this article as recorded by

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Hormonal and metabolic profiles of obese and nonobese type 2 diabetes patients: implications of plasma insulin, ghrelin, and vitamin D levels
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Association of obesity in T2DM with differential polymorphism of ghrelin, growth hormone secretagogue receptor-1 and telomeres maintenance genes
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Leu72Met and Other Intronic Polymorphisms in theGHRLandGHSRGenes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population
Faris Elbahi Joatar, Ali Ahmed Al Qarni, Muhalab E. Ali, Abdulaziz Al Masaud, Abdirashid M. Shire, Nagalla Das, Khalid Gumaa, Hayder A. Giha
Endocrinology and Metabolism.2017; 32(3): 360. CrossRef
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