A Pilot Study Investigating the Influence of Glucagon-Like Peptide-1 Receptor Single Nucleotide Polymorphisms on Gastric Emptying Rate in Caucasian Men.

Adora M W Yau,William Gilmore,Gethin H Evans,Ronald J Maughan,John Mclaughlin,Jason J Ashworth

doi:10.3389/fphys.2018.01331

Abstract

Gastric emptying rate in humans is subject to large individual variability, but previous research on the influence of genetics is scarce. Variation in the glucagon-like peptide-1 receptor (GLP1R) gene is a plausible candidate gene to partially explain the high variance. This study aimed to investigate the influence of genetic variation in the GLP1R gene on gastric emptying rate of a glucose solution in humans. Forty eight healthy Caucasian males took part in this investigation. Gastric emptying rate of a 6% glucose solution was assessed using the 13C breath test method and a venous blood sample was obtained from each participant. Participants were genotyped for 27 Tag single nucleotide polymorphisms (SNPs) in the GLP1R locus using Sequenom MassARRAY iPLEX GOLD analysis and MALDI-TOF mass spectrometry. The time at which maximal emptying rate occurred (Tlag) was faster in participants with the CC genotype than in TT and TC genotypes for SNP rs742764: [median (quartiles) CC, 35 (30–36) min vs. TT, 43 (39–46) min, and TC, 41 (39–45) min; P < 0.01]. Tlag was also slower in participants with the AA genotype compared to the TT and TA genotypes for SNP rs2254336: [AA, 43 (39–49) min vs. TT, 36 (34–41) min, and TA, 39 (35–42) min; P < 0.05]. Analysis by phenotype also showed differences in half-emptying time (T12) and Tlag for SNPs rs9283907, rs2268657, and rs2254336. Several neighboring Tag SNPs within the GLP1R gene were found to be associated with gastric emptying rate, and should be further investigated.

Highlights

An increasing number of genetic variants within the genes coding for gastrointestinal hormones and their receptors are being found to be associated with obesity phenotypes, appetite, and food regulation
No variants occurred among the participants for three single nucleotide polymorphisms (SNPs), Tag SNP 3 within the promoter region and two of the three selected missense polymorphism, SNPs and
No significant differences in gastric emptying rate were seen between genotypes for all other SNPs, T1/2 tended toward significance for SNP 9 rs9283907 (P = 0.054) and Tlag tended to significance for SNP 5 rs2268657 (P = 0.087) and SNP 15 rs7766663 (P = 0.076)

Summary

Introduction

An increasing number of genetic variants within the genes coding for gastrointestinal hormones and their receptors are being found to be associated with obesity phenotypes, appetite, and food regulation. Research on the potential influence of genetics on gastric emptying rate is scarce. Acosta et al (2014) reported a common genetic variant rs17782313 in the Melanocortin 4 receptor (MC4R) gene, which has previously been found to be strongly associated with common obesity (Loos et al, 2008; Vogel et al, 2011), to be associated with reduced gastric emptying rate and satiation. Cremonini et al (2005) found an association between the 779T > C polymorphism in the cholecystokinin (CCK) gene and slower gastric emptying rate. On the other hand, Jones et al (2010) found no effect of common genetic polymorphisms of the CCK or CCK-1 receptor genes on gastric emptying rate

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