Impact of common polymorphisms in candidate genes for insulin resistance and obesity on weight loss of morbidly obese subjects after laparoscopic adjustable gastric banding and hypocaloric diet

J Clin Endocrinol Metab. 2005 Sep;90(9):5064-9. doi: 10.1210/jc.2005-0404. Epub 2005 Jun 28.

Abstract

Context: It is unknown whether genetic factors that play an important role in body weight homeostasis influence the response to laparoscopic adjustable gastric banding (LAGB).

Objective: We investigated the impact of common polymorphisms in four candidate genes for insulin resistance on weight loss after LAGB.

Design: The design was a 6-month follow-up study.

Setting: The study setting was hospitalized care.

Patients: A total of 167 unrelated morbidly obese subjects were recruited according to the following criteria: age, 18-66 yr inclusive; and body mass index greater than 40 kg/m2 or greater than 35.0 kg/m2 in the presence of comorbidities.

Intervention: LAGB was used as an intervention.

Main outcome measure: Measure of correlation between weight loss and common polymorphisms in candidate genes for insulin resistance and obesity was the main outcome measure.

Results: The following single nucleotide polymorphisms were detected by digestion of PCR products with appropriate restriction enzymes: Gly972Arg of the insulin receptor substrate-1 gene, Pro12Ala of the proliferator-activated receptor-gamma gene, C-174G in the promoter of IL-6 gene, and G-866A in the promoter of uncoupling protein 2 gene. Baseline characteristics including body mass index did not differ between the genotypes. At the 6-month follow-up after LAGB, carriers of G-174G IL-6 genotype had lost more weight than G-174C or C-174C genotype (P = 0.037), and carriers of A-866A uncoupling protein 2 genotype had lost more weight as compared with G-866G (P = 0.018) and G-866A (P = 0.035) genotype, respectively. Weight loss was lower in carriers of Gly972Arg insulin receptor substrate-1 genotype than Gly972Gly carriers, but not statistically significant (P = 0.06). No difference between carriers of Pro12Ala and Pro12Pro proliferator-activated receptor-gamma genotype was observed.

Conclusions: These data demonstrate that genetic factors, which play an important role in the regulation of body weight, may account for differences in the therapeutic response to LAGB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diet, Reducing*
  • Female
  • Follow-Up Studies
  • Gastroplasty*
  • Heterozygote
  • Humans
  • Insulin Receptor Substrate Proteins
  • Insulin Resistance / genetics*
  • Interleukin-6 / genetics
  • Ion Channels
  • Male
  • Membrane Transport Proteins / genetics
  • Middle Aged
  • Mitochondrial Proteins / genetics
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / surgery*
  • PPAR gamma / genetics
  • Phosphoproteins / genetics
  • Polymorphism, Single Nucleotide*
  • Postoperative Period
  • Uncoupling Protein 2
  • Weight Loss / genetics*

Substances

  • IRS1 protein, human
  • Insulin Receptor Substrate Proteins
  • Interleukin-6
  • Ion Channels
  • Membrane Transport Proteins
  • Mitochondrial Proteins
  • PPAR gamma
  • Phosphoproteins
  • UCP2 protein, human
  • Uncoupling Protein 2