Leptin and leptin receptor gene polymorphisms in obese and healthy children

Year 2022, Volume: 47 Issue: 1, 71 - 78, 31.03.2022

Ayça Kanat Yarım Khayala Rasulova Gönül Çatlı Tuncay Küme Ayhan Abacı Sefa Kızıldağ

https://doi.org/10.17826/cumj.977534

Cited By: 2

Abstract

Purpose: The of this study is to explore the differences between leptin (LEPG2548A), which is considered efficacious in respect of adiposity and leptin receptor gene variants (LEPRQ223R, K109R, K656N). Furthermore, the relationship between these differences and the serum leptin level shall be scrutinized.
Materials and Methods: A total of 300 volunteers (12-17 years of age) joined our study (150controls–150obese). Blood samples obtained from these individuals were used for DNA isolation. An examination was carried out in order to show polymorphisms of the leptin receptor gene increased by RealTime PCR previously. The variations of the leptin gene were ascertained by implementation of restriction fragment length polymorphism method.
Results: Genotype dispersion calculations led to the understanding that the AA-genotype was lower in the K109R polymorphism control group than in the patient group, whereas AG-genotype was higher. The control group of Q223R polymorphism had higher AA-genotype values than the patient group, whereas it showed lower AG-genotype values. Moreover, anthropometric and metabolic results were found to be significantly higher (p in the patient group than in the control group.
Conclusion: The patient group of LEPRQ223R polymorphism showed lower AA-genotype values, a higher AG-genotype dispersion and a higher allele-G value. Therefore, a relationship to adiposity has been assumed. 

Keywords

Leptin, leptin receptor, obesity, polymorphism.

Supporting Institution

Dokuz Eylül Üniversitesi Tıp Fakültesi Bilimsel Araştırma Projeleri Birimi

Project Number

2019.KB.SAG.014.

Thanks

The study was supported by the Dokuz Eylul University Scientific Research Projects Coordination (DEUTF BAP).

Obez ve sağlıklı çocuklarda leptin ve leptin reseptör gen polimorfizmleri

Abstract

Amaç: Bu çalışmada obezitede etkili olduğu düşünülen leptin (LEP G-2548A) ve leptin reseptör gen (LEPR Q223R, LEPR K109R ve LEPR K656N tek nükleotid polimorfizmleri) varyantlarındaki farklılıkların araştırılması amaçlanmıştır. Ayrıca bu farklılıkların serum leptin düzeyi ile olan ilişkisinin incelenmesi planlanmıştır.
Gereç ve Yöntem: Çalışmamıza toplam 300 (150 obez çocuk, 150 sağlıklı çocuk) gönüllü (12-17 yaş aralığında) katılmıştır. Bu kişilerden alınan kan örneklerinden DNA izolasyonu yapılmıştır. İzole edilen DNA örnekleri RealTime PCR ile çoğaltılmış leptin reseptör geninde polimorfizm bakılmıştır. Leptin genindeki varyasyon ise restriksiyon fragment uzunluk polimorfizmi yöntemiyle saptanmıştır.
Bulgular: Genotip dağılım hesaplamaları sonucunda K109R polimorfizminin kontrol grubunda AA genotipin hasta grubuna göre düşük, AG genotipin ise yüksek görüldüğü belirlenmiştir. Q223R polimorfizminin kontrol grubunda AA genotipin hasta grubuna göre yüksek, AGgenotipin ise düşük olduğu görülmüştür. K656N ve G2548A polimorfizmlerinin hasta ve kontrol gruplarındaki genotip dağılımlarında belirgin bir farklılık bulunamamıştır. Dahası antropometrik ve metabolik sonuçların hasta grubunda kontrol grubuna göre anlamlı derecede yüksekolduğu tespit edilmiştir.
Sonuç: LEPR Q223R polimorfizminin hasta grupta AA genotipinin daha düşük, AG genotipinin daha yüksek dağılımı ve G allelinin daha yüksek oranla görülmüştür. Bu nedenle obeziteyle ilişkili olabileceği düşünülmüştür. 

Keywords

leptin, leptin reseptör, obezite, polimorfizm

Project Number

2019.KB.SAG.014.

References

• Szymanski MW, Singh DP. Isoproterenol. StatPearls. Treasure Island , FL, StatPearls Publishing LLC. 2021.
• Lalitha G, Poornima P, Archanah A, Padma VV. Protective effect of neferine against isoproterenol-induced cardiac toxicity. Cardiovasc Toxicol. 2013;13:168-79.
• Jiang T, Han F, Gao G, Liu M. Mangiferin exert cardioprotective and anti-apoptotic effects in heart failure induced rats. Life Sci. 2020;249:117476.
• Rajadurai M, Prince PS. Preventive effect of naringin on isoproterenol-induced cardiotoxicity in Wistar rats: an in vivo and in vitro study. Toxicology. 2007;232:216-25.
• Matera MG, Page C, Rinaldi B. β2-Adrenoceptor signalling bias in asthma and COPD and the potential impact on the comorbidities associated with these diseases. Curr Opin Pharmacol. 2018;40:142-46.
• Davel AP, Kawamoto EM, Scavone C, Vassallo DV, Rossoni LV. Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation. Br J Pharmacol. 2006;148:629-39.
• Fleming I, Busse R. Molecular mechanisms involved in the regulation of the endothelial nitric oxide synthase. Am J Physiol Regul Integr Comp Physiol. 2003;284:R1-12.
• Ross R. Atherosclerosis--an inflammatory disease. N Engl J Med. 1999;340:115-26.
• Darakhshan S, Bidmeshki Pour A, Hosseinzadeh Colagar A, Sisakhtnezhad S. Thymoquinone and its therapeutic potentials. Pharmacol Res. 2015;95-96:138-58.
• Khan MA, Tania M, Fu J. Epigenetic role of thymoquinone: impact on cellular mechanism and cancer therapeutics. Drug Discov Today. 2019;24:2315-22.
• Li F, Rajendran P, Sethi G. Thymoquinone inhibits proliferation, induces apoptosis and chemosensitizes human multiple myeloma cells through suppression of signal transducer and activator of transcription 3 activation pathway. Br J Pharmacol. 2010;161:541-54.
• Xu C, Tang F, Lu M, Yang J, Han R, Mei M et al. Astragaloside IV improves the isoproterenol-induced vascular dysfunction via attenuating eNOS uncoupling-mediated oxidative stress and inhibiting ROS-NF-κB pathways. Int Immunopharmacol. 2016;33:119-27.
• Satake N, Shibata M, Shibata S. Endothelium- and cytochrome P-450-dependent relaxation induced by isoproterenol in rat aortic rings. Eur J Pharmacol. 1997;319:37-41.
• Davel AP, Fukuda LE, De Sá LL, Munhoz CD, Scavone C, Sanz-Rosa D et al. Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta. Am J Physiol Heart Circ Physiol. 2008;295:H211-9.
• Boarescu PM, Chirilă I, Bulboacă AE, Bocșan IC, Pop RM, Gheban D et al. Effects of curcumin nanoparticles in isoproterenol-induced myocardial infarction. Oxid Med Cell Longev. 2019;2019:7847142.
• Khan MS, Gohar A, Abbas G, Mahmood W, Rauf K, Sewell RD. Thymoquinone inhibition of acquisition and expression of alcohol-induced behavioral sensitization. Phytother Res. 2015;29:1610-5.
• Karabulut D, Akin AT, Unsal M, Lekesizcan A, Ozyazgan TM, Keti DB et al. L-Carnitine ameliorates the liver by regulating alpha-SMA, iNOS, HSP90, HIF-1alpha, and RIP1 expressions of CCL4-toxic rats. Iran J Basic Med Sci. 2021;24:184-90.
• Karabulut D, Sonmez MF. Effects of diabetes on nitric oxide synthase in rat uterus. Biotech Histochem. 2020:1-8.
• Karabulut D, Ozturk E, Kuloglu N, Akin AT, Kaymak E, Yakan B. Effects of vitamin B12 on methotrexate hepatotoxicity: evaluation of receptor-interacting protein (RIP) kinase. Naunyn Schmiedebergs Arch Pharmacol. 2020;393:2473-80.
• Clapp BR, Hingorani AD, Kharbanda RK, Mohamed-Ali V, Stephens JW, Vallance P et al. Inflammation-induced endothelial dysfunction involves reduced nitric oxide bioavailability and increased oxidant stress. Cardiovasc Res. 2004;64:172-8.
• Desjardins MP, Sidibé A, Fortier C, Mac-Way F, De Serres S, Larivière R et al. Impact of kidney transplantation on aortic stiffness and aortic stiffness index β0. J Hypertens. 2019;37:1521-28.
• Marais L, Franck G, Allaire E, Zidi M. Diameter and thickness-related variations in mechanical properties of degraded arterial wall in the rat xenograft model. J Biomech. 2016;49:3467-75.
• Cantini C, Kieffer P, Corman B, Limiñana P, Atkinson J, Lartaud-Idjouadiene I. Aminoguanidine and aortic wall mechanics, structure, and composition in aged rats. Hypertension. 2001;38:943-8.
• Cha HN, Hong GR, Kim YW, Kim JY, Dan JM, Park SY. Deficiency of iNOS does not prevent isoproterenol-induced cardiac hypertrophy in mice. Korean J Physiol Pharmacol. 2009;13:153-9.
• Szabó C, Haskó G, Zingarelli B, Németh ZH, Salzman AL, Kvetan V et al. Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. Immunology. 1997;90:95-100.
• Feng W, Li W. The study of ISO induced heart failure rat model. Exp Mol Pathol. 2010;88:299-304.
• Madhur MS, Lob HE, McCann LA, Iwakura Y, Blinder Y, Guzik TJ et al. Interleukin 17 promotes angiotensin II-induced hypertension and vascular dysfunction. Hypertension. 2010;55:500-7.
• S M, Shaik AH, E MP, Al Omar SY, Mohammad A, Kodidhela LD. Combined cardio-protective ability of syringic acid and resveratrol against isoproterenol induced cardio-toxicity in rats via attenuating NF-kB and TNF-α pathways. Sci Rep. 2020;10:3426.
• Morimoto K, Kitano T, Eguchi R, Otsuguro K. Bidirectional modulation of TNF-α transcription via α- and β-adrenoceptors in cultured astrocytes from rat spinal cord. Biochem Biophys Res Commun. 2020;528:78-84.
• Viswanadha VP, Dhivya V, Beeraka NM, Huang CY, Gavryushova LV, Minyaeva NN et al. The protective effect of piperine against isoproterenol-induced inflammation in experimental models of myocardial toxicity. Eur J Pharmacol. 2020;885:173524.
• Luan A, Tang F, Yang Y, Lu M, Wang H, Zhang Y. Astragalus polysaccharide attenuates isoproterenol-induced cardiac hypertrophy by regulating TNF-α/PGC-1α signaling mediated energy biosynthesis. Environ Toxicol Pharmacol. 2015;39:1081-90.
• Randhawa MA, Alghamdi MS, Maulik SK. The effect of thymoquinone, an active component of Nigella sativa, on isoproterenol induced myocardial injury. Pak J Pharm Sci. 2013;26:1215-9.
• Ojha S, Azimullah S, Mohanraj R, Sharma C, Yasin J, Arya DS et al. Thymoquinone protects against myocardial ischemic injury by mitigating oxidative stress and inflammation. Evid Based Complement Alternat Med. 2015;2015:143629.
• Ozer EK, Goktas MT, Toker A, Pehlivan S, Bariskaner H, Ugurluoglu C et al. Thymoquinone protects against the sepsis induced mortality, mesenteric hypoperfusion, aortic dysfunction and multiple organ damage in rats. Pharmacol Rep. 2017;69:683-90.
• El-Agamy DS, Nader MA. Attenuation of oxidative stress-induced vascular endothelial dysfunction by thymoquinone. Exp Biol Med (Maywood). 2012;237:1032-8.
• Zhu N, Xiang Y, Zhao X, Cai C, Chen H, Jiang W et al. Thymoquinone suppresses platelet-derived growth factor-BB-induced vascular smooth muscle cell proliferation, migration and neointimal formation. J Cell Mol Med. 2019;23:8482-92.
• Niazmand S, Fereidouni E, Mahmoudabady M, Mousavi SM. Endothelium-independent vasorelaxant effects of hydroalcoholic extract from Nigella sativa seed in rat aorta: the roles of Ca2+ and K+ channels. Biomed Res Int. 2014;2014:247054.
• Karabulut D, Ozturk E, Kaymak E, Akin AT, Yakan B. Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 2021;35:e22618.