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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

Dipartimento di Medicina Sperimentale e Clinica (G.S., F.A., C.R., M.L.H.), Università Magna Græcia di Catanzaro, 88100 Catanzaro, Italy; Divisione di Medicina Interna (L.P., P.V., V.G., M.M., F.F.), Divisione di Chirurgia Generale (M.P., G.F.), Istituto di Ricovero e Cura a Carattere Scientifico Ospedale San Raffaele, 20132 Milano, Italy; Department of Internal Medicine (M.C., M.L.H.), University of Rome-Tor Vergata, 00133 Rome, Italy; and Universitá di Milano, Cattedra di Medicina Interna and Seconda Divisione di Medicina Interna, Ospedale San Paolo (A.E.P.), 20142 Milano, Italy

Address all correspondence and requests for reprints to: Giorgio Sesti, M.D., Dipartimento Medicina Sperimentale e Clinica, Università Magna-Græcia di Catanzaro, Via Campanella, 115, 88100 Catanzaro, Italy. E-mail: sesti{at}unicz.it; or Franco Folli, M.D., Ph.D., Department of Internal Medicine, HS Raffaele, Via Olgettina 60, 20132 Milan, Italy. E-mail: folli.franco{at}hsr.it.

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- 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- 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.

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