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Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort

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Abstract

Leptin is a protein hormone synthesized by adipocytes and is involved in the regulation of food intake and energy expenditure. We hypothesized that any change in the promoter sequence can affect the expression of the gene and hence leptin protein levels in the serum. The aim of the current study was to investigate the relationship of such a promoter variant of the leptin gene, G-2548A polymorphism, with obesity and its effect on various anthropometric and metabolic parameters in a Pakistani cohort consisting of 250 obese and 225 non-obese control subjects. Body weight, height, waist circumference (WC), hip circumference (HC) and blood pressure (BP) were measured by standard methods and levels of fasting blood glucose (FBG), total cholesterol, triglycerides, HDLC, LDLC, and leptin were determined. Genotyping was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The results showed that the LEP G-2548A polymorphism showed significant association with obesity in Pakistan. In addition, the polymorphism showed association with weight, height, BMI, WC, HDLC and serum leptin levels. The findings suggest that the leptin promoter G-2548A variant may play its part in the progression to obesity by not only affecting the body’s fat distribution but also by changing the serum leptin and HDLC levels.

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References

  • Baptista T, Sandia I, Fernandez E, Balzán L, Connell L, Uzcátegui E, Serrano A, Pabón A, et al. 2015 Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder. Rev. Bras. Psiquiatr. 37 106–112

    PubMed  Google Scholar 

  • Constantin A, Costache G, Sima AV, Glavce CS, Vladica M and Popov DL 2010 Leptin G-2548A and leptin receptor Q223R gene polymorphisms are not associated with obesity in Romanian subjects. Biochem. Biophys. Res. Commun. 391 282–286

    Article  CAS  PubMed  Google Scholar 

  • Cordell HJ 2009 Detecting gene–gene interactions that underlie human diseases. Nat. Rev. Genet. 10 392–404

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Franek E, Nowak J, Safranow K, Adler G, Bińczak-Kuleta A, Ciechanowicz A and Więcek A 2010 G (-2548) A leptin gene polymorphism in obese subjects is associated with serum leptin concentration and bone mass. Pol. Arch. Med. Wewn. 120 175–180

    CAS  PubMed  Google Scholar 

  • Klop B, Elte JWF and Cabezas MC 2013 Dyslipidemia in obesity: mechanisms and potential targets. Nutrients 5 1218–1240

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Le Stunff C, Le Bihan C, Schork NJ and Bougnères P 2000 A common promoter variant of the leptin gene is associated with changes in the relationship between serum leptin and fat mass in obese girls. Diabetes 49 2196–2200

    Article  PubMed  Google Scholar 

  • Li K, Liu Y, Venners SA, Hsu Y-H, Jiang S, Weinstock J, Sun Y, Wang B and Xu X 2016 Effects of LEP G2548A and LEPR Q223R polymorphisms on serum lipids and response to simvastatin treatment in Chinese patients with primary hyperlipidemia. Clin Appl Thromb Hemost 1076029616638504

  • Liu Y, Liu Z, Song Y, Zhou D, Zhang D, Zhao T, Chen Z, Yu L, et al. 2010 Metaanalysis added power to identify variants in FTO associated with type 2 diabetes and obesity in the Asian population. Obesity 18 1619–1624

    Article  CAS  PubMed  Google Scholar 

  • Luke A, Guo X, Adeyemo A, Wilks R, Forrester T, Lowe W Jr, Comuzzie A, Martin L, et al. 2001 Heritability of obesity-related traits among Nigerians, Jamaicans and US black people. Int. J. Obes. Relat. Metab. Disord. 25 1034–1041

    Article  CAS  PubMed  Google Scholar 

  • Mammès O, Betoulle D, Aubert R, Giraud V, Tuzet S, Petiet A, Colas-Linhart N and Fumeron F 1998 Novel polymorphisms in the 5'region of the LEP gene: association with leptin levels and response to low-calorie diet in human obesity. Diabetes 47 487–489

    Article  PubMed  Google Scholar 

  • Manolio TA, Collins FS, Cox NJ, Goldstein DB, Hindorff LA, Hunter DJ, McCarthy MI, Ramos EM, et al. 2009 Finding the missing heritability of complex diseases. Nature 461 747–753

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sacks FM and Campos H 2003 Clinical review 163: cardiovascular endocrinology: Low-density lipoprotein size and cardiovascular disease: a reappraisal. J. Clin. Endocrinol. Metab. 88 4525–4532

    Article  CAS  PubMed  Google Scholar 

  • Shabana and Hasnain S 2015a Association of the leptin receptor Gln223Arg polymorphism with lipid profile in obese Pakistani subjects. Nutrition 31 1136–1140

    Article  CAS  PubMed  Google Scholar 

  • Shabana and Hasnain S 2015b The fatty acid binding protein 2 (FABP2) polymorphism Ala54Thr and obesity in Pakistan: a population based study and a systematic meta-analysis. Gene. 574 106–111. doi:10.1016/j.gene.2015.07.087

    Article  CAS  PubMed  Google Scholar 

  • Shabana and Hasnain S 2016a Obesity, more than a ‘cosmetic’ problem. Current knowledge and future prospects of human obesity genetics. Biochem. Genet. 54 1–28

    Article  CAS  PubMed  Google Scholar 

  • Shabana and Hasnain S 2016b The p. N103K mutation of Leptin (LEP) gene and severe early onset obesity in Pakistan. Biol. Res. 2016 23

    Article  Google Scholar 

  • Shabana, Shahid SU, Li KW, Acharya J, Cooper J, Hasnain S and Humphries SE (2015) Effect of six type 2 diabetes susceptibility loci and an FTO variant on Obesity in Pakistani subjects. Eur J Hum Genet In Press. doi:10.1038/ejhg.2015.212

  • Suriyaprom K, Tungtrongchitr R and Thawnasom K 2014 Measurement of the levels of leptin, BDNF associated with polymorphisms LEP G2548A, LEPR Gln223Arg and BDNF Val66Met in Thai with metabolic syndrome. Diabetol. Metab. Syndr. 6 1–9

    Article  Google Scholar 

  • Zhang Y, Proenca R, Maffei M, Barone M, Leopold L and Friedman JM 1994 Positional cloning of the mouse obese gene and its human homologue. Nature 372 425–432

    Article  CAS  PubMed  Google Scholar 

  • Zhang F, Basinski MB, Beals JM, Briggs SL, Churgay LM, Clawson DK, DiMarchi RD, Furman TC, et al. 1997 Crystal structure of the obese protein Ieptin-E100

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Acknowledgements

The Higher Education Commission (HEC) of Pakistan is acknowledged for providing financial support for the study under Indigenous 5000 program (Batch VII PIN#bm7-153).

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Correspondence to Shabana.

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Corresponding editor: Sarah H Elsea

[Shabana and Hasnain S 2016 Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort. J. Biosci.] DOI 10.1007/s12038-016-9612-2

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Shabana, Hasnain, S. Leptin promoter variant G2548A is associated with serum leptin and HDL-C levels in a case control observational study in association with obesity in a Pakistani cohort. J Biosci 41, 251–255 (2016). https://doi.org/10.1007/s12038-016-9612-2

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