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Heterozygosity for the rs696217 SNP in the Preproghrelin Gene Predicts Weight Loss After Bariatric Surgery in Severely Obese Individuals

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Abstract

Background

Several patients encompass a scarce weight loss after Roux-en-Y gastric bypass (RYGB). As such event is not related to surgical complications, finding markers able to identify “well responders” and to predict weight loss outcome is clinically relevant. Ghrelin regulates appetite and energy balance. Common single nucleotide polymorphisms (SNPs) in its encoding genes have been associated with body weight regulation. Other peptides involved in satiety modulation, like the CD40/CD40L complex, are less explored.

Methods

One hundred, otherwise healthy, obese subjects (aged 45 ± 11 years, 65 females, BMI 48.0 ± 0.7 kg/m2) were sequentially enrolled in years 2014–2015. SNPs rs2241766 for adiponectin gene, rs490683 for ghrelin receptor, rs696217 and rs27647 for the preproghrelin/ghrelin gene, and rs1126535 for the CD40L gene were determined on DNA extracted from circulating lymphomonocytes. Patients were reevaluated at 6 (n = 100), 26 (n = 91), and 52 weeks (n = 79) after RYGB.

Results

Subjects carrying the rs696217 T allele encompassed a significantly greater reduction in BMI 52 weeks after surgery (GG vs GT 30.5 ± 1.1 vs 38.1 ± 2.1 %; p < 0.001). Carrying the rs1126535 C allele in the CD40L gene was associated with a significantly lower BMI reduction at week 52 (TT vs CT 33.2 ± 1.1 vs 28.1 ± 2.3 %, p = 0.049). rs490683 and rs27647 SNPs of ghrelin and rs2241766 for adiponectin gene did not show any difference between carriers and non-carriers of the mutant allele.

Conclusion

Carrying a G to T substitution in rs696217 (preproghrelin gene) seems to mark a successful weight loss outcome; we also report for the first time that the rs1126535 C allele (CD40L gene) may predict a worse response to bariatric surgery.

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Authors and Affiliations

  1. Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy

    Edoardo Vitolo, Eleonora Santini, Marta Seghieri, Livia Giannini, Chiara Rossi, Angela Dardano & Anna Solini

  2. Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy

    Fabio Coppedè

Authors
  1. Edoardo Vitolo
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  2. Eleonora Santini
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  3. Marta Seghieri
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  4. Livia Giannini
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  5. Fabio Coppedè
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  6. Chiara Rossi
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  7. Angela Dardano
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  8. Anna Solini
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Correspondence to Anna Solini.

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Grant Information and Support

This study has been supported by an institutional grant of the University of Pisa.

Conflict of Interest

The authors declare that hey have no conflict of interest.

Ethical Statement

The protocol was approved by the Ethics Committee of the University of Pisa (n3463/2011).

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All participants in this study read and signed an informed consent.

Additional information

E. Vitolo and E. Santini share the first authorship

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Vitolo, E., Santini, E., Seghieri, M. et al. Heterozygosity for the rs696217 SNP in the Preproghrelin Gene Predicts Weight Loss After Bariatric Surgery in Severely Obese Individuals. OBES SURG 27, 961–967 (2017). https://doi.org/10.1007/s11695-016-2387-6

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