Ethnicity-Specific Association Between Ghrelin Leu72Met Polymorphism and Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Huang, Rong; Tian, Sai; Cai, Rongrong; Sun, Jie; Shen, Yanjue; Wang, Zhanpeng

doi:10.3389/fgene.2018.00541

Cited by 9 publications

(7 citation statements)

References 52 publications

(109 reference statements)

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“…The frequency for the T allele found in this study is closer to the one (19.1%) reported in East Asian populations [28]. One plausible explanation for the discrepancy between these results is that these studies have focused on European populations, but not on the Balkans [26,[28][29][30]; the present study is the first to report rs696217 allele frequencies among Greek healthy controls.…”

Section: Discussionsupporting

confidence: 51%

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome

et al. 2020

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Introduction/Objective: Irritable bowel syndrome (IBS) is a bowel disorder characterized by pain accompanying defecation or altered bowel habits, divided into diarrhea-predominant, constipation-predominant, and alternating subtypes, whose pathogenesis is considered to include disordered bowel motility. The hormone ghrelin is a growth hormone secretagogue which furthermore affects gastrointestinal motility. We study the association between its genetic polymorphisms and the risk for IBS. Methods: IBS patients meeting the Rome III criteria and controls similar in age and gender were recruited. Whole blood samples were used for genotyping via polymerase chain reaction and restriction fragment length polymorphism for the polymorphisms rs34911341, rs696217, and rs2075356. Results: Participants included 142 patients and 209 controls. The rs696217 GG genotype frequency was higher in patients (78.87%) compared to controls (55.5%). The rs696217 GT genotype was significantly less frequent among patients than in controls (OR 0.31, 95% CI 0.19–0.52), as was the T allele (OR 0.43, 95% CI 0.28–0.66). No significant differences in genotype distribution were found for the rs34911341 and rs2075356 polymorphisms between patients and controls. The genotype frequencies did not significantly differ between IBS subtype groups for any of the polymorphisms studied. Conclusions: The GG and GT genotypes of the rs696217 polymorphism, as well as the G-allele, demonstrate significant association with IBS susceptibility, while the T allele appears to bear a protective effect. Ghrelin’s polymorphisms are plausibly involved in IBS pathogenesis, but do not correlate with any distinct IBS subtype.

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Section: Discussionsupporting

confidence: 51%

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome

et al. 2020

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“…Recent meta-analysis study by Huang et al . [ 41 ] reported that the GHRL gene Leu72Met variation was possibly protective against T2DM in Caucasians and predisposing in Asians. The consequence of c.214G>T polymorphism is the amino acid substitution Leu72Met.…”

Section: Discussionmentioning

confidence: 99%

“…Moreover, Steinle et al [40] reported that Met72 allele was associated with metabolic syndrome as well as higher fasting glucose, LDL-C and higher triglyceride levels in the Old Order Amish population. Recent meta-analysis study by Huang et al [41] reported that the GHRL gene Leu72Met variation was possibly protective against T2DM in Caucasians and predisposing in Asians. The consequence of c.214G>T polymorphism is the amino acid substitution Leu72Met.…”

Section: Discussionmentioning

confidence: 99%

Dual effect of the GHRL gene variant in the molecular pathogenesis of obesity

Becer

Ergoren

2021

Balkan Journal of Medical Genetics

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Obesity is as a global health problem due to its interaction with complex chronic disorders such as cardiovascular disorders, type 2 diabetes mellitus (T2DM) and cancer. Despite the fact that pathogenesis of obesity is not yet clearly understood, it is associated with a combination of psychological, environmental and various genetic factors. Here, employing a case-control design, we aimed to examine the effects of the GHRL c.152C>T (p.Arg51Gln) (rs34911341) and c.214G>T (p.Leu72Met) (rs696217) markers on susceptibility to obesity in a Turkish-Cypriot population, as well as to evaluate whether these markers affect biochemical parameters and show their putative functional consequences. This study involved 211 Turkish-Cypriot subjects (106 obese and 95 non obese). Genotyping for the GHRL gene polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis. Our results indicate that the GHRL Leu72Met polymorphism was found to be significantly higher in obese patients, with respect to genotypic (p = 0.0012) and allelic (p = 0.0005) frequencies. Strikingly, the rs696217 GT genotype (heterozygous) had significantly lower serum high-density lipoprotein cholesterol (HDL-C) (p = 0.015) than GG (wild type) genotypes. Overall, Leu72Met susceptibility variant may be considered as risk and crucial marker for both obesity and cholesterol metabolism in the community of Turkish-Cypriots. Thus, the dual effect of the GHRL gene Leu72Met variant may be used for clinical diagnosis.

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“…All of this evidence contributes to the controversial role of this polymorphism in T2D, where its effects in susceptibility varies in different ethnic groups as it has also been described for other human features. It is known that in humans, approximately 15% of the SNP's are population-specific and the differences could be due to the different proportions of SNP alleles in a specific population [16,32]. But at the moment, the underlying mechanisms of molecular evolution of this SNP between different populations is unclear.…”

Section: Discussionmentioning

confidence: 99%

“…The Leu72Met polymorphism consists of a transversion of an Cytosine for an Adenine in the position 247 of the GHRL gene, consequently leading to an amino acid change (missense) from Leucine to Methionine in codon 72 [15]. It is known that there is a differential effect of this polymorphism in terms of T2D susceptibility among different ethnic groups [16], so far, there is no evidence about genotypic and allelic frequencies and their association with T2D and in serum ghrelin levels in Mexican population.…”

Section: Introductionmentioning

confidence: 99%

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population

et al. 2020

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Background: Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied. Methods: The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a casecontrol study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant. Results: Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23-0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population. Conclusions: The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.

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Ethnicity-Specific Association Between Ghrelin Leu72Met Polymorphism and Type 2 Diabetes Mellitus Susceptibility: An Updated Meta-Analysis

Cited by 9 publications

References 52 publications

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome

Ghrelin Gene Polymorphisms in Irritable Bowel Syndrome

Dual effect of the GHRL gene variant in the molecular pathogenesis of obesity

Leu72Met polymorphism of GHRL gene decreases susceptibility to type 2 diabetes mellitus in a Mexican population

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