Association of genetic variants of ghrelin, leptin and UCP2 with malnutrition inflammation syndrome and survival in end-stage renal disease patients

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• 作者：Richa Sharma (1)
  Suraksha Agrawal (2)
  Anita Saxena (1)
  Manmohan Pandey (3)
  R. K. Sharma (1)
  
• 关键词：End ; stage renal disease ; Malnutrition inflammation syndrome ; Leptin ; Ghrelin UCP2
• 刊名：Genes & Nutrition
• 出版年：2013
• 出版时间：November 2013
• 年：2013
• 卷：8
• 期：6
• 页码：611-621
• 全文大小：
• 作者单位：Richa Sharma (1)
  Suraksha Agrawal (2)
  Anita Saxena (1)
  Manmohan Pandey (3)
  R. K. Sharma (1)
  
  1. Department of Nephrology, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Raebareli Road, Lucknow, 226014, UP, India
  2. Department of Medical Genetics, SGPGIMS, Lucknow, India
  3. School of Telemedicine and Biomedical Informatics, SGPGIMS, Lucknow, India
  
• ISSN：1865-3499

文摘

Malnutrition inflammation syndrome (MIS) is common among ESRD patients. In the present study, we have investigated the association of genetic markers associated with appetite and energy regulation with malnutrition inflammation syndrome among end-stage renal disease (ESRD) patients. Two hundred and fifty-seven patients on maintenance hemodialysis and 200 normal healthy controls were included in the study. Nutritional assessment was done by subjective global assessment scores (SGA). Genotyping of leptin-2548 G/A (rs7799039), ghrelin Leu72Met (rs696217-408 C/A), Arg51Gln (rs34911341-346 G/A) and uncoupling protein 2 (UCP2) 45bp insertion deletion was done using PCRFLP. Levels of leptin and acyl ghrelin were assessed using ELISA. Leptin-2548 AA genotype was associated with twofold higher risk of disease susceptibility while UCP2 insertioneletion heterozygotes showed protective effect. Ghrelin Gln51Gln and Met72Met genotype were associated with 3.4- and 2.5-fold higher disease susceptibility. The Met72 and Gln51 allele showed 3.3- and 2.1-fold higher susceptibility to malnutrition in severe SGA group. Further, the levels of acyl ghrelin were significantly less in severe category of malnutrition and in poor appetite group. On combined analysis, the group 2 (presence of 3 risk alleles) showed 1.5- and twofold higher susceptibility to disease and malnutrition, respectively. On docking analysis, it was observed that higher receptor binding energy was associated with the mutant form of ghrelin (Gln51). Moderate and severe SGA were associated with 2.2- and 4.1-fold higher death hazard. Our study suggests that ghrelin may be major marker contributing to susceptibility to MIS among ESRD patients.