<i>IRX3</i> is a genetic modifier for birth weight, adolescent obesity and transaminase metabolism

Liu, C.; Chu, Chenyu; Zhang, J.; Wu, Dan; Xu, Dong-ping; Li, P.; Chen, Yongsheng; Liu, B.; Liu, Pei; Zhang, L.; Liu, S.; Qi, Tongyun; Lou, Xiaohuan; Li, L.

doi:10.1111/ijpo.12214

Cited by 11 publications

(6 citation statements)

References 29 publications

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“…A 10% increase in overweight or obesity frequency was found when rs3751723 genotype changed from GG to TT. This result coincides with recent studies from multiple populations in which the IRX3 genomic region has been related to anthropometric traits and obesity 14,28,36 . Considering that this gene has been identified as a plausible effector for the influence of FTO on bodyweight [10][11][12][13] , the current genetic associations might be evidence supporting the biological role of IRX3 on weight control as it has been suggested in animal models 12,13 .…”

Section: Discussionsupporting

confidence: 92%

“…Se encontró un aumento del 10% en la frecuencia de sobrepeso u obesidad cuando el genotipo rs3751723 cambió de GG a TT. Este resultado coincide con estudios recientes de múltiples poblaciones en los que la región genómica IRX3 se ha relacionado con rasgos antropométricos y obesidad 14 , 28 , 36 ). Teniendo en cuenta que este gen ha sido identificado como un efector plausible para la influencia de FTO en el peso corporal ( 10 - 13 ), las asociaciones genéticas actuales podrían ser evidencia que apoya el papel biológico de IRX3 en el control de peso, como se ha sugerido en modelos animales 12 , 13 .…”

Section: Discussionunclassified

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Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess

et al. 2022

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Background: Fat Mass and Obesity-related (FTO) has been one of the genes consistently related to common obesity. Single nucleotide polymorphisms (SNPs) in FTO have been linked with the IRX3 gene. Aim: This study was designed by testing the hypothesis that: i) common SNPs in FTO and IRX3 are associated with obesity and related disorders; ii) there is significant linkage disequilibrium between both genes. Methods: A cross-sectional study was carried out on the Colombian Caribbean Coast. Anthropometric and biochemical variables were measured, and obesity and metabolic disorders were diagnosed. Four SNPs were genotyped: 3 at FTO locus (rs17817449, rs8050136, rs9939609) and one at IRX3 locus (rs3751723). LD between these SNPs was estimated. A logistic regression model was applied to estimate associations. Results: A total of 792 subjects were included. FTO and IRX3 were not in LD (D’≤ 0.03; R2≤ 0.03). TT genotype (rs9939609) was found to be associated with waist circumference (p= 0.04; adj-p=0.01), and IRX3 SNP with Body Weight Excess (BWE) (OR= 1.06, adj-p= 0.03). One FTO-IRX3 haplotype was associated with BWE (G-A-A-T, rs17817449-rs8050136-rs9939609-rs3751723; OR= 0.67, p= 0.04). The statistical significance of these relations continued after admixture adjustment for a three-hybrid population (p= 0.03). Conclusions: FTO was related to waist circumference, and IRX3 was associated with BWE in Latin American adults. This relation remained statistically significant after performing an adjustment for sex, age, and genetic ancestry. Despite these genes not being in LD, findings of a haplotype involving FTO-IRX3 suggest a gene-gene interaction associated with an increased risk of BWE.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionunclassified

Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess

et al. 2022

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“…It was observed that there was a relationship between IRX3, new-born birth weight and body max index (BMI). Genotypes rs8053360 CC and rs1126960 GG were related to body weight and BMI, particularly among females [29]. In another study by Srivastava et al , participants were divided into two groups (overweight and normal weight subjects) in order to investigate the relationship between IRX3 and obesity.…”

Section: Resultsmentioning

confidence: 99%

The possible mechanisms of the effects of IRX3 gene on body weight: an overview

Jarrahi

Akbari

Rezaei

et al. 2019

Arch Med Sci Atheroscler Dis

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IntroductionRecent studies reported that FTO exert its effects on body weight through change the expression IRX3. The aim of this study was investigation of the possible mechanisms of the effects of IRX3 gene on obesity.Material and methodsThe present review was carried out using keywords such as polymorphism and/or obesity and/or BMI and/or IRX3 gene and/or Iroquois homeobox protein 3. Databases including PubMed, Science Direct, web of sciences, Scopus, and Cochran databases were used to collect all related articles published from 2000 to 2019.ResultsBased on this review, there are some evidences on the association between the IRX3 polymorphisms and the IRX3 expression level with body weight. In some studies, the up-regulation of IRX3 expression was related to increased body weight, while in some other studies down-regulation of IRX3 expression was related to obesity.ConclusionsThis review investigated the probable mechanisms of the effects of the IRX3 gene on obesity. Studies in this are limited and reported contradictory results. Further studies are required to evaluate the role of IRX3 gene in the associations between genes, diet, and obesity.

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“…It was also observed that there was a relationship between IRX3 , newborn birth weight and BMI. Genotypes rs8053360 CC and rs1126960 GG were related to body weight and BMI, particularly among female individuals ( 46 ), and the polymorphism rs3751723 in IRX3 has been associated with obesity ( 47 ). In the present study, immunohistochemical staining and RNA-seq results from liver tissue showed that the expression of IRX3 was decreased in MAFLD patients.…”

Section: Discussionmentioning

confidence: 99%

IRX3 plays an important role in the pathogenesis of metabolic-associated fatty liver disease by regulating hepatic lipid metabolism

Chen

et al. 2022

Front. Endocrinol.

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Metabolic-associated fatty liver disease (MAFLD) affects approximately a quarter of the global population. Identification of the key genes and pathways involved in hepatic lipid metabolism is of the utmost importance for the diagnosis, treatment, and prevention of MAFLD. In this study, differentially expressed genes were identified through whole-genome transcriptional analysis of liver tissue from MAFLD patients and healthy controls, and a series of lipid metabolism-related molecules and pathways were obtained through pathway analysis. Subsequently, we focused on Iroquois homeobox protein 3 (IRX3), one of 13 transcription factors that were screened from the 331 differentially expressed genes. The transcription factor IRX3 was significantly decreased in the liver tissue of patients with MAFLD when compared with healthy controls. Pearson’s correlation analysis showed that the expression levels of IRX3 in liver tissue were negatively correlated with serum total cholesterol, triglycerides, low-density lipoprotein cholesterol, and uric acid levels. The overexpression and interference of IRX3 induced the increased and decreased lipid droplet accumulation in vitro, respectively. Moreover, interference of IRX3 expression increased mitochondrial fragmentation and reduced the activity of the mitochondrial respiratory chain complex IV. In summary, the study demonstrated that IRX3 regulated hepatic lipid metabolism of MAFLD, and also revealed the effect of IRX3 on mitochondria might be an important mechanism by which IRX3 regulated hepatic lipid metabolism of MAFLD.

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IRX3 is a genetic modifier for birth weight, adolescent obesity and transaminase metabolism

Abstract: IRX3 genetic variants associate with birth weight, BMI and AST/ALT-related transaminase metabolism, supporting the role of IRX3 as an obesity-associated susceptibility gene.

Cited by 11 publications

References 29 publications

Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess

Interaction analysis of FTO and IRX3 genes with obesity and related metabolic disorders in an admixed Latin American population: a possible risk increases of body weight excess

The possible mechanisms of the effects of IRX3 gene on body weight: an overview

IRX3 plays an important role in the pathogenesis of metabolic-associated fatty liver disease by regulating hepatic lipid metabolism

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