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



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.



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.



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.
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Edoardo
E
Vitolo
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Eleonora
E
Santini
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Marta
M
Seghieri
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Livia
L
Giannini
Department of Translational Research and New Technologies in Medicine and Surgery, Section of Medical Genetics, University of Pisa, Pisa, Italy.
Fabio
F
Coppedè
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Chiara
C
Rossi
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy.
Angela
A
Dardano
Department of Clinical and Experimental Medicine, University of Pisa, I-56126, Pisa, Italy. anna.solini@med.unipi.it.
Anna
A
Solini
D052242:Adiponectin / Q000235:genetics; D000328:Adult; D015415:Biomarkers; D023201:CD40 Ligand / Q000235:genetics*; D005260:Female; D015390:Gastric Bypass; D054439:Ghrelin / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009767:Obesity, Morbid / Q000235:genetics* / Q000601:surgery*; D020641:Polymorphism, Single Nucleotide; D054440:Receptors, Ghrelin / Q000235:genetics; D015431:Weight Loss / Q000235:genetics*; D055815:Young Adult
C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D054439:Ghrelin; D054440:Receptors, Ghrelin; D023201:CD40 Ligand
Ghrelin/preproghrelin; Polymorphisms; Predictors; Weight loss outcome; sCD40L
BMC Med Genet. 2011 Jan 10;12:5
21219602
Horm Metab Res. 2009 Jan;41(1):55-61
18949681
Genes Immun. 2015 Sep;16(6):399-404
26043172
Psychiatr Genet. 2007 Feb;17(1):13-6
17167339
Peptides. 2011 Nov;32(11):2319-22
21527298
Eur J Clin Invest. 2006 Jun;36(6):395-401
16684123
Eur Eat Disord Rev. 2015 Nov;23(6):504-8
26608946
Osteoporos Int. 2011 May;22(5):1451-8
20577873
Obesity (Silver Spring). 2009 Apr;17(4):745-54
19165163
PLoS One. 2008 Aug 13;3(8):e2941
18698404
J Am Coll Cardiol. 2009 Aug 18;54(8):669-77
19679244
Obes Surg. 2015 Sep;25(9):1741-9
26112137
Obes Res. 2002 Aug;10(8):782-91
12181387
BMC Genet. 2015 Oct 16;16:121
26474561
Obes Surg. 2012 May;22(5):783-90
22411573
Int J Obes (Lond). 2006 Dec;30(12):1702-8
16607383
Endocr Dev. 2013;25:91-100
23652395
Int J Endocrinol Metab. 2015 Jul 01;13(3):e19073
26425125
JAMA Surg. 2013 Feb;148(2):151-6
23426590
Stroke. 2015 Jul;46(7):1990-2
26012640
Am J Physiol Endocrinol Metab. 2013 May 1;304(9):E951-63
23482447
J Pharmacol Sci. 2006;100(5):398-410
16612045
J Clin Endocrinol Metab. 2002 Aug;87(8):4005-8
12161552
Clin Chim Acta. 2008 Jan;387(1-2):42-7
17884032
Cell Metab. 2013 Feb 5;17(2):185-96
23352188
Eat Weight Disord. 2015 Dec;20(4):513-8
26122195
Curr Med Chem. 2012;19(32):5467-73
22876924
Clin Med Res. 2010 Jul;8(2):89-95
20660932
Diabet Med. 2006 Jun;23(6):685-9
16759313
Acta Biochim Biophys Sin (Shanghai). 2007 Dec;39(12):974-81
18064390
Genet Mol Biol. 2014 Mar;37(1):15-22
24688286
Int J Obes (Lond). 2008 Apr;32(4):663-8
18071345
Cell Metab. 2007 Jul;6(1):55-68
17618856
Eur J Endocrinol. 2004 Jul;151(1):127-33
15248833
Thromb Res. 2007;119(1):79-84
16476470