Correlational studies on insulin resistance and leptin gene polymorphisms in peritoneal dialysis patients

Document Type : Original Article


Department of Nephrology, Molecular Cell Laboratory for Kidney Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Center for Peritoneal Dialysis Research, Shanghai, China


Objective(s):The aim of the study was to investigate the relationship between insulin resistance (IR) and leptin (LEP) gene polymorphisms in peritoneal dialysis (PD) patients.
Materials and Methods: From July 1, 2011 to August 1, 2011, patients who received chronic PD were chosen and divided into three groups (DM, high HOMR-IR, and low HOMR-IR). Two PCR products of LEP were sequenced and aligned and the distribution of polymorphisms was analyzed using χ2 analysis. In addition, serum leptin level, PD conditions, and biochemical parameters according to different genotype of G-2548A and A19G were statistically analyzed (P-value<0.05). The relationship between LEP gene polymorphisms and prognosis was explored.
Results: Totally 157 patients with average age of 55±15 years old were chosen. Distribution of genotype frequencies was complied with Hardy-Weinberg equilibrium. Leptin level and BMI (body mass index) of the GG genotype of G-2548A were higher than that of GA or AA. The fasting glucose, cholesterol, etc. of AA genotype were lower, and the nPCR was higher than the two other genotypes. Serum leptin level and BMI of AA genotype of A19G was higher than GA and GG genotypes; meanwhile, fasting blood glucose of that genotypes was the highest. In addition, survival rate of AA group of A19G was very low.
Conclusion:The G-2548A and A19G polymorphisms were correlated with serum leptin level and IR. Leptin A19G polymorphism may be prognostic for PD patients. This study may facilitate early intervention for IR in PD patients.


1. Isse N, Ogawa Y, Tamura N, Masuzaki H, Mori K, Okazaki T, et al. Structural organization and chromosomal assignment of the human obese gene. J Biol Chem 1995; 270:27728-27733.
2. de Luis DA, Aller R, Izaola O, Conde R, Bouza JE. Lys656Asn Polymorphism of leptin receptor gene is rtelated with leptin changes after a high monounsaturated fat diet in obese patients. J Invest Med 2013; 61:286-290.
3. Ovsyannikova IG, White SJ, Larrabee BR, Grill DE, Jacobson RM, Poland GA. Leptin and leptin-related gene polymorphisms, obesity, and influenza A/H1N1 vaccine-induced immune responses in older individuals. Vaccine 2014; 32:881-887.
4. Kohan L, Nasiri M, Habib A, Bolhasani A. Association of G-2548A polymorphism in the promoter of leptin gene with plasma leptin level and risk of Type 2 Diabetes. JSSU 2013; 21:70-77.
5. Ribeiro R, Vasconcelos A, Costa S, Pinto D, Morais A, Oliveira J, et al. Overexpressing leptin genetic polymorphism (−2548 G/A) is associated with susceptibility to prostate cancer and risk of advanced disease. Prostate 2004; 59:268-274.
6. Hager J, Clement K, Francke S, Dina C, Raison J, Lahlou N, et al. A polymorphism in the 5'untranslated region of the human ob gene is associated with low leptin levels. Int J Obes Relat Metab Disord 1998; 22:200-205.
7. Ohshiro Y, Ueda K, Nishi M, Ishigame M, Wakasaki H, Kawashima H, et al. A polymorphic marker in the leptin gene associated with Japanese morbid obesity. J Mol Med 2000; 78:516-520.
8. Lakka TA, Rankinen T, Weisnagel SJ, Chagnon YC, Lakka H-M, Ukkola O, et al. Leptin and leptin receptor gene plymorphisms and changes in glucose homeostasis in response to regular exercise in nondiabetic individuals The HERITAGE Family Study. Diabetes 2004; 53:1603-1608.
9. Mammes O, Betoulle D, Aubert R, Herbeth B, Siest G, Fumeron F. Association of the G-2548A polymorphism in the 5′ region of the LEP gene with overweight. Ann Hum Gene 2000; 64:391-394.
10. Van der Lende T, Te Pas M, Veerkamp R, Liefers S. Leptin gene polymorphisms and their phenotypic associations. Vitam Horm 2005; 71:373-404.
11. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387:903-908.
12. Le Stunff C, Le Bihan C, Schork NJ, Bougnères P. 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 2000; 49:2196-2200.
13. Ren W, Zhang S-H, Wu J, Ni Y-X. Polymorphism of the leptin gene promoter in pedigrees of type 2 diabetes mellitus in Chongqing, China. Chin Med J 2004; 117:558-561.
14. Simpson S, Raubenheimer D. The protein leverage hypothesis in human obesity. Ann Nutr Metab 2007; 51:6-36.
15. Cao L, Mou S, Fang W, Gu L, Huang J, Gu A, Qian J, Ni Z. Hyperleptinemia, insulin resistance and survival in peritoneal dialysis patients. Nephrology 2015; 20:617-624.
16. Gawkrodger D, Ferguson A, Barnetson R. Nutritional status in patients with dermatitis herpetiformis.  Am J Clin Nutr 1988; 48:355-360.
17. Mazen I, El-Gammal M, Abdel-Hamid M, Amr K. A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient. Mol Genet Metab 2009; 97:305-308.
18. Lönnqvist F, Arner P, Nordfors L, Schalling M. Overexpression of the obese (ob) gene in adipose tissue of human obese subjects. Nat Med 1995; 1:950-953.
19. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372:425-432.
20. Considine RV, Considine EL, Williams C, Nyce MR, Magosin SA, Bauer T, et al. Evidence against either a premature stop codon or the absence of obese gene mRNA in human obesity. J Clin Invest 1995; 95:2986.
21. Hinuy HM, Hirata MH, Forti N, Diament J, Sampaio MF, Armaganijan D, et al. Leptin G-2548A promoter polymorphism is associated with increased plasma leptin and BMI in Brazilian women. Arq Bras Endocrinol Metabol 2008;52:611-616.
22. Ma D, Feitosa MF, Wilk JB, Laramie JM, Yu K, Leiendecker-Foster C, et al. Leptin is associated with blood pressure and hypertension in women from the National Heart, Lung, and Blood Institute Family Heart Study. Hypertension 2009; 53:473-479.