GLP-1R polymorphism (rs1042044) and expression are associated with the risk of papillary thyroid cancer among the Egyptian population

Abdul-Maksoud, Rehab S.; Elsayed, Walid S.H.; Rashad, Nearmeen M.; Elsayed, Rasha S; Elshorbagy, Shereen; Hamed, Mohamed G.

doi:10.1016/j.gene.2022.146597

Cited by 6 publications

(3 citation statements)

References 42 publications

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“…GLP-1R rs1042044 was found to be associated with morning salivary cortisol levels in preschoolers [ 13 ], reward learning, and anhedonia [ 14 ]. A study also reported that the rs1042044 C>A polymorphism may influence the risk of papillary thyroid cancer by affecting GLP-1R expression [ 15 ]. Additionally, GLP-1R rs2268641 has been linked to obesity-related traits in European Americans [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms in the glucagon-like peptide-1 receptor gene and their interactions on the risk of osteoporosis in postmenopausal Chinese women

Liu,

Bao,

Tian

et al. 2023

PLoS ONE

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Postmenopausal osteoporosis (PMOP) is a prevalent form of primary osteoporosis, affecting over 40% of postmenopausal women. Previous studies have suggested a potential association between single nucleotide polymorphisms (SNPs) in glucagon-like peptide-1 receptor (GLP-1R) and PMOP in postmenopausal Chinese women. However, available evidence remains inconclusive. Therefore, this study aimed to investigate the possible association between GLP-1R SNPs and PMOP in Han Chinese women. Thus, we conducted a case-control study with 152 postmenopausal Han Chinese women aged 45–80 years, including 76 women with osteoporosis and 76 without osteoporosis. Seven SNPs of the GLP-1R were obtained from the National Center of Biotechnology Information and Genome Variation Server. We employed three genetic models to assess the association between GLP-1R genetic variants and osteoporosis in postmenopausal women, while also investigating SNP-SNP and SNP-environment interactions with the risk of PMOP. In this study, we selected seven GLP-1R SNPs (rs1042044, rs2268641, rs10305492, rs6923761, rs1126476, rs2268657, and rs2295006). Of these, the minor allele A of rs1042044 was significantly associated with an increased risk of PMOP. Genetic model analysis revealed that individuals carrying the A allele of rs1042044 had a higher risk of developing osteoporosis in the dominant model (P = 0.029, OR = 2.76, 95%CI: 1.09–6.99). Furthermore, a multiplicative interaction was found between rs1042044 and rs2268641 that was associated with osteoporosis in postmenopausal women (Pinteraction = 0.034). Importantly, this association remained independent of age, menopausal duration, family history of osteoporosis, and body mass index. However, no significant relationship was observed between GLP-1R haplotypes and PMOP. In conclusion, this study suggests a close association between the A allele on the GLP-1R rs1042044 and an increased risk of PMOP. Furthermore, this risk was significantly augmented by an SNP-SNP interaction with rs2268641. These results provide new scientific insights into the development of personalized prevention strategies and treatment approaches for PMOP.

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Section: Discussionmentioning

confidence: 99%

Polymorphisms in the glucagon-like peptide-1 receptor gene and their interactions on the risk of osteoporosis in postmenopausal Chinese women

Liu,

Bao,

Tian

et al. 2023

PLoS ONE

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“…As rare missense variant SNPs with a high frequency of MAF in GLP-1R, rs1042044 and rs3765467 are often the focus of research. Although rs1042044 had nothing to do with insulin secretion [ 15 ], it was reported to be associated with susceptibility of T2DM in a Chinese literature [ 19 ] and the risk of papillary thyroid cancer among the Egyptian population in a recent study [ 44 ]. Moreover, rs1042044 was also differentially associated with brain functional connectivity in individuals with low versus high severity of alcohol use [ 45 ].…”

Section: Discussionmentioning

confidence: 99%

Genetic variants of the GLP-1R gene affect the susceptibility and glucose metabolism of gestational diabetes mellitus: a two-center nested case‒control study

Luo

Fan

Xiong

et al. 2022

Diabetol Metab Syndr

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Background Gestational diabetes mellitus (GDM) is the most common complication during pregnancy, occurring under the combined action of environmental and genetic factors. Genetic variants of glucagon-like peptide-1 receptor (GLP-1R) have been reported to affect insulin secretion and susceptibility to type 2 diabetes. This study aimed to explore the role of GLP-1R polymorphisms in GDM and glucose metabolism. Methods A two-center nested case‒control study was designed, including 200 pregnant women with GDM and 200 pregnant women without GDM genotyped for five tag SNPs of GLP-1R using Sanger sequencing. Logistic regression was used to evaluate the relationship between GLP-1R polymorphisms and GDM risk. Glucose and insulin concentrations were measured based upon the 75 g oral glucose tolerance test (OGTT). Beta cell function of different genotypes was estimated with the 60 min insulinogenic index (IGI60) and OGTT-derived disposition index (DI). Results Mutant genotype AG + GG of tag SNP rs6458093 nominally increased GDM risk (p = 0.049), especially among subjects younger than 35 years (p = 0.024) and with BMI no less than 24 (p = 0.041), after adjusting for confounders. Meanwhile, compared with subjects with wild genotype AA, subjects with genotype AG + GG of rs6458093 also showed nominally significantly lower IGI60 (p = 0.032) and DI (p = 0.029), as well as significantly higher 75 g OGTT-based 1 h glucose load plasma glucose levels (p = 0.045). Moreover, the mutant heterozygous genotype GA of tag SNP rs3765467 nominally decreased GDM risk among subjects older than 35 years (p = 0.037) but showed no association with insulin secretion and glucose homeostasis. Conclusions Tag SNP rs6458093 of GLP-1R was nominally associated with increased GDM risk and affected beta cell function and postprandial glucose metabolism, while tag SNP rs3765467 of GLP-1R was nominally associated with decreased GDM risk, providing evidence for molecular markers and etiological study of GDM.

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“…5 In addition, GLP-1 receptors are expressed in human papillary thyroid carcinoma (PTC) cells 17 to a greater extent than in normal human thyroid cells. 18 Although GLP-1 receptor genetic polymorphism tissue expression has been linked to an increase in PTC incidence and invasiveness, 19 a significant effect of GLP-1RA agonists on the proliferation of PTC cells has not been demonstrated. 18 The pathophysiological rationale for a potential increase in the risk of thyroid cancer determined by GLP-1RA treatment cannot therefore be considered firmly established.…”

Section: Introductionmentioning

confidence: 99%

Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials

Silverii,

Monami,

Gallo

et al. 2023

Diabetes Obesity Metabolism

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AimTo conduct a meta‐analysis of randomized clinical trials (RCTs) to investigate whether there is an association between glucagon‐like peptide‐1 receptor agonist (GLP‐1RA) treatment and thyroid cancer.Materials and MethodsIn this meta‐analysis of RCTs, we included studies comparing a GLP‐1RA with any comparator, lasting at least 52 weeks, and reporting the incidence of adverse events independently of the principal endpoint and population. All cases of thyroid cancer were collected.ResultsWe retrieved 64 trials, 26 of which reported at least one incident case of thyroid cancer. GLP‐1RA treatment was associated with a significant increase in the risk of overall thyroid cancer (Mantel‐Haenzel odds ratio [MH‐OR] 1.52 [95% confidence interval {CI} 1.01, 2.29]; P = 0.04, I2 = 0%), with a fragility index of 1, and a 5‐year number needed to harm of 1349. The association remained significant when including only trials lasting at least 104 weeks (MH‐OR 1.76 [95% CI 1.00, 3.12]; P = 0.05). No significant association was found for papillary thyroid cancer (MH‐OR 1.54 [95% CI 0.77, 3.06]; P = 0.22) or medullary thyroid cancer (MH‐OR 1.44 [95% CI 0.23, 9.16]; P = 0.55).ConclusionsOur meta‐analysis showed that GLP‐1RA treatment could be associated with a moderate increase in relative risk for thyroid cancer in clinical trials, with a small increase in absolute risk. Studies of longer duration are required to assess the clinical implications of this finding.

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GLP-1R polymorphism (rs1042044) and expression are associated with the risk of papillary thyroid cancer among the Egyptian population

Cited by 6 publications

References 42 publications

Polymorphisms in the glucagon-like peptide-1 receptor gene and their interactions on the risk of osteoporosis in postmenopausal Chinese women

Polymorphisms in the glucagon-like peptide-1 receptor gene and their interactions on the risk of osteoporosis in postmenopausal Chinese women

Genetic variants of the GLP-1R gene affect the susceptibility and glucose metabolism of gestational diabetes mellitus: a two-center nested case‒control study

Glucagon‐like peptide‐1 receptor agonists and risk of thyroid cancer: A systematic review and meta‐analysis of randomized controlled trials

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