Endocrinol Metab.  2017 Sep;32(3):360-369. 10.3803/EnM.2017.32.3.360.

Leu72Met and Other Intronic Polymorphisms in the GHRL and GHSR Genes Are Not Associated with Type 2 Diabetes Mellitus, Insulin Resistance, or Serum Ghrelin Levels in a Saudi Population

• Joatar FE
• Al Qarni A
• Ali ME
• Al Masaud
• Shire AM
• Das N
• Gumaa K
• Giha HA

• KMID: 2389817
• DOI: http://doi.org/10.3803/EnM.2017.32.3.360

Abstract

BACKGROUND
Ghrelin (GHRL), a gastric peptide encoded by the GHRL gene, is known to be involved in energy homeostasis via its G protein receptor, encoded by the growth hormone secretagogue receptor (GHSR) gene. Some studies have shown associations between plasma GHRL levels and GHRL single-nucleotide polymorphisms (SNPs), namely the Leu72Met polymorphism (rs696217 TG), with type 2 diabetes mellitus (T2DM) and insulin resistance (IR), while others have not. The controversies in these associations raise the issue of "˜which SNPs in which populations.' The aim of this study was to investigate whether SNPs in GHRL and/or GHSR genes were associated with T2DM, IR, or plasma GHRL levels among Arab Saudis.
METHODS
Blood was collected from 208 Saudi subjects with (n=107) and without (n=101) T2DM. DNA samples from these subjects were analyzed by real-time polymerase chain reaction to genotype five intronic SNPs in the GHRL (rs696217 TG, rs27647 CT, rs2075356 CT, and rs4684677 AT) and GHSR (rs509030 GC) genes. In addition, plasma GHRL levels were measured by a radioimmunoassay.
RESULTS
None of the SNPs were associated with T2DM, IR, or plasma GHRL levels. The frequencies of the alleles, genotypes, and haplotypes of the five SNPs were comparable between the T2DM patients and the non-diabetic subjects. A large number of the GHRL haplotypes indicates the molecular heterogeneity of the preproghrelin gene in this region.
CONCLUSION
Neither the Leu72Met polymorphism nor the other intronic GHRL and GHSR SNPs were associated with T2DM, IR, or GHRL levels. Further investigations should be carried out to explain the molecular basis of the association of the GHRL peptide with T2DM and IR.

Keyword

Diabetes mellitus, type 2; Insulin resistance; Ghrelin; Receptors, ghrelin; Polymorphism

MeSH Terms

Alleles
Arabs
Diabetes Mellitus, Type 2*
DNA
Genotype
Ghrelin*
GTP-Binding Proteins
Haplotypes
Homeostasis
Humans
Insulin Resistance*
Insulin*
Introns*
Plasma
Polymorphism, Single Nucleotide
Population Characteristics
Radioimmunoassay
Real-Time Polymerase Chain Reaction
Receptors, Ghrelin
DNA
GTP-Binding Proteins
Ghrelin
Insulin
Receptors, Ghrelin

Figure

• 

  Fig. 1 Linkage disequilibrium analyses of ghrelin single-nucleotide polymorphisms (SNPs; rs2075356, rs696217, rs27647, rs3755777) and a growth hormone secretagogue receptor (GHSR) SNP (rs509030 GC). The strength of the linkage is indicated by the value of D′, and the maximum value (absolute linkage) is 100%. The GHSR SNP had the least linkage with the other ghrelin SNPs.

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