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Muhalab E. Ali  (Ali ME) 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
  • 5,044 View
  • 49 Download
  • 9 Web of Science
  • 13 Crossref
AbstractAbstract PDFPubReader   
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

Citations to this article as recorded by  
  • Exploring the Role of Metabolic Hormones in Amyotrophic Lateral Sclerosis
    Anca Moțățăianu, Ion Bogdan Mănescu, Georgiana Șerban, Laura Bărcuțean, Valentin Ion, Rodica Bălașa, Sebastian Andone
    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
  • Effect of the GHRL gene (rs696217) polymorphism on the metabolic disorders in patients with obesity in the Ukrainian population
    Andrii Prodan, Ihor Dzubanovsky, Oleksandr Kamyshnyi, Natalia Melnyk, Stepan Grytsenko, Stanislava Voloshyn
    Endocrine Regulations.2023; 57(1): 173.     CrossRef
  • Impact of gene polymorphism of glutathione S-transferase and ghrelin as a risk factor in Egyptian women with gestational diabetes mellitus
    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
  • Investigation of GHRL (rs4684677), FTO (rs8044769) and PGC1Α (rs8192678) polymorphisms in type 2 diabetic Turkish population
    Osman Oğuz, Arezoo Gheybi, Zeliha Doğan, Feray Akbaş, Ümit Zeybek, Arzu Ergen
    Turkish Journal of Biochemistry.2022; 47(5): 564.     CrossRef
  • Grelin ve Grelin Reseptörü Polimorfizmlerinin Tip 2 Diyabetle İlişkisi
    Esma SELÇUK, Uğur ŞAHİN, Didem ÖZKAHRAMAN, Mustafa CALAPOĞLU, Nilüfer ŞAHİN CALAPOĞLU
    Süleyman Demirel Üniversitesi Sağlık Bilimleri Dergisi.2022; 13(2): 218.     CrossRef
  • Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study
    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
    Journal of Personalized Medicine.2022; 12(5): 735.     CrossRef
  • Variation analysis of Ghrelin gene in Chinese patients with obesity, having polycystic ovarian syndrome
    Xiaomeng Wang, Fengxiang Qu, Chunlian Wang, Yan Wang, Dan Wang, Min Zhao, Xiangbing Yun, Qingmei Zheng, Lin Xu
    Gynecological Endocrinology.2020; 36(7): 594.     CrossRef
  • The flavonoid baicalin improves glucose metabolism by targeting the PH domain of AKT and activating AKT/GSK3β phosphorylation
    Shengnan Yang, Yuan Zhang, Fukui Shen, Xiaoyao Ma, Man Zhang, Yuanyuan Hou, Gang Bai
    FEBS Letters.2019; 593(2): 175.     CrossRef
  • 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
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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
  • 5,752 View
  • 56 Download
  • 21 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   
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  
  • 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
  • Hormonal and metabolic profiles of obese and nonobese type 2 diabetes patients: implications of plasma insulin, ghrelin, and vitamin D levels
    Hayder A. Giha, Dhuha M. B. AlDehaini, Faris E. Joatar, Muhalab E. Ali, Einas M. Al-Harbi, Ali A. Al Qarni
    Cardiovascular Endocrinology & Metabolism.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
  • TLR4 mutation protects neurovascular function and cognitive decline in high-fat diet-fed mice
    Nathalie Obadia, Giulia Andrade, Marina Leardini-Tristão, Letícia Albuquerque, Celina Garcia, Flavia Lima, Júlio Daleprane, Hugo C. Castro-Faria-Neto, Eduardo Tibiriçá, Vanessa Estato
    Journal of Neuroinflammation.2022;[Epub]     CrossRef
  • Differential Association of Selected Adipocytokines, Adiponectin, Leptin, Resistin, Visfatin and Chemerin, with the Pathogenesis and Progression of Type 2 Diabetes Mellitus (T2DM) in the Asir Region of Saudi Arabia: A Case Control Study
    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
    Journal of Personalized Medicine.2022; 12(5): 735.     CrossRef
  • C-peptide is a predictor of telomere shortening: A five-year longitudinal study
    Racha Ghoussaini, Hani Tamim, Martine Elbejjani, Maha Makki, Lara Nasreddine, Hussain Ismaeel, Mona P. Nasrallah, Nathalie K. Zgheib
    Frontiers in Endocrinology.2022;[Epub]     CrossRef
  • Relationship Between Acyl and Desacyl Ghrelin Levels with Insulin Resistance and Body Fat Mass in Type 2 Diabetes Mellitus
    Pu Zang, Cui-Hua Yang, Jun Liu, Hai-Yan Lei, Wei Wang, Qing-Yu Guo, Bin Lu, Jia-Qing Shao
    Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy.2022; Volume 15: 2763.     CrossRef
  • The Association of Pre-Transplant C-Peptide Level with the Development of Post-Transplant Diabetes: A Cohort Study
    Amanda J. Vinson, Aran Thanamayooran, Bryce A. Kiberd, Kenneth West, Ferhan S. Siddiqi, Lakshman Gunaratnam, Karthik K. Tennankore
    Kidney360.2022; 3(10): 1738.     CrossRef
  • Secondary analysis of gut hormone data from children with and without in utero exposure to gestational diabetes: Differences in the associations among ghrelin, GLP‐1, and insulin secretion
    Ayse G. Zengul, Sarah ET Hoover, Paula C. Chandler‐Laney
    Pediatric Obesity.2021;[Epub]     CrossRef
  • The Links of Ghrelin to Incretins, Insulin, Glucagon, and Leptin After Bariatric Surgery
    Daria Skuratovskaia, Maria Vulf, Nataliya Chasovskikh, Aleksandra Komar, Elena Kirienkova, Egor Shunkin, Pavel Zatolokin, Larisa Litvinova
    Frontiers in Genetics.2021;[Epub]     CrossRef
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    Сергей Николаевич Чернуха , Ирина Александровна Вильцанюк
    Естественные и Технические Науки.2021; (№05): 220.     CrossRef
  • Variation analysis of Ghrelin gene in Chinese patients with obesity, having polycystic ovarian syndrome
    Xiaomeng Wang, Fengxiang Qu, Chunlian Wang, Yan Wang, Dan Wang, Min Zhao, Xiangbing Yun, Qingmei Zheng, Lin Xu
    Gynecological Endocrinology.2020; 36(7): 594.     CrossRef
  • Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population
    Edgar Alfonso Rivera-León, Mara Anaís Llamas-Covarrubias, Sergio Sánchez-Enríquez, Erika Martínez-López, Mercedes González-Hita, Iris Monserrat Llamas-Covarrubias
    BMC Endocrine Disorders.2020;[Epub]     CrossRef
  • Ghrelin Levels and Decreased Kidney Function in Patients with Early Stages of Chronic Kidney Disease Against the Background of Obesity
    Nataliia Vasylivna Gubina, Iryna Hryhorivna Kupnovytska, Vasyl Hryhorovych Mishchuk, Halyna Dmytrivna Markiv
    Journal of Medicine and Life.2020; 13(4): 530.     CrossRef
  • Ghrelin fiber projections from the hypothalamic arcuate nucleus into the dorsal vagal complex and the regulation of glycolipid metabolism
    Manqing Su, Meixing Yan, Yanling Gong
    Neuropeptides.2019; 78: 101972.     CrossRef
  • Ghrelin deficiency in patients with type 2 diabetes: the relationships with obesity, adipose tissue dysfunction and glucose variability
    V V Klimontov, D M Bulumbaeva, O N Fazullina, N B Orlov, V I Konenkov
    Terapevticheskii arkhiv.2019; 91(10): 28.     CrossRef
  • The Correlation Between Circulating Ghrelin and Insulin Resistance in Obesity: A Meta-Analysis
    Cai-Shun Zhang, Liu-Xin Wang, Rui Wang, Yuan Liu, Li-Min Song, Jun-Hua Yuan, Bin Wang, Jing Dong
    Frontiers in Physiology.2018;[Epub]     CrossRef
  • Biomarker potential of C-peptide for screening of insulin resistance in diabetic and non-diabetic individuals
    Haseeb A. Khan, Samia H. Sobki, Aishah Ekhzaimy, Isra Khan, Mona A. Almusawi
    Saudi Journal of Biological Sciences.2018; 25(8): 1729.     CrossRef
  • 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
  • Expanded Normal Weight Obesity and Insulin Resistance in US Adults of the National Health and Nutrition Examination Survey
    Keilah E. Martinez, Larry A. Tucker, Bruce W. Bailey, James D. LeCheminant
    Journal of Diabetes Research.2017; 2017: 1.     CrossRef
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