Association between 14 bp insertion/deletion
            <i>HLA‐G</i>
            functional polymorphism and insulin resistance in a cohort of Italian children with obesity

Marzuillo, Pierluigi; Bellini, Giulia; Punzo, Francesca; Sessa, Anna Di; Guarino, Stefano; Umano, Giuseppina Rosaria; Toraldo, R; Giudice, Emanuele Miraglia del

doi:10.1111/pedi.12768

Cited by 8 publications

(7 citation statements)

References 19 publications

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“…At the same time, the expression level of nonclassical HLA-class I molecule G (HLA-G) is downregulated in childhood obesity and in obese adolescents with insulin resistance these changes were more significant. Recently, it was shown that there is a strong association between HLA-G 14 bp ins/ins genotype and insulin resistance in obese children and adolescents (Marzuillo et al 2018), but at the same time, there were identified two opposite sides of HLA-G function: beneficial to be promoted or deleterious to be blocked (Amiot et al 2015;Carosella et al 2015). Thus, additional studies may be necessary to determine the functional significance of HLA-G gene expression in obese subjects both with and without insulin resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, the dual role of HLA-G in solid and liquid tumors was shown: HLA-G inhibits the proliferation of malignant B cells due to the interaction between HLA-G and its receptor ILT2, which mediates negative signaling on B cell proliferation (Rouas-Freiss et al 2014). Recently, it was shown that there is a strong association between HLA-G 14 bp ins/ins genotype and insulin resistance (evaluated by homeostasis model assessment [HOMA]) in obese children and adolescents (Marzuillo et al 2018).…”

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confidence: 99%

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Insulin resistance in obese adolescents affects the expression of genes associated with immune response

Minchenko

2019

Endocrine Regulations

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Objective. The development of obesity and its metabolic complications is associated with dysregulation of various intrinsic mechanisms, which control basic metabolic processes through changes in the expression of numerous regulatory genes.Methods. The expression level of HLA-DRA, HLA-DRB1, HLA-G, HLA-F, and NFX1 genes as well as miR-190b was measured in the blood of obese adolescents without signs of resistance to insulin and with insulin resistance in comparison with the group of relative healthy control individuals without signs of obesity.Results. It was shown that obesity without signs of insulin resistance is associated with upregulation of the expression level of HLA-DRA and HLA-DRB1 genes, but with down-regulation of HLA-G gene expression in the blood as compared to control group of relative healthy adolescents. At the same time, no significant changes were observed in the expression level of HLA-F and NFX1 genes in the blood of this group of obese adolescents. Development of insulin resistance in obese individuals leads to significant down-regulation of HLA-DRA, HLA-DRB1, HLA-G, and HLA-F gene expressions as well as to up-regulation of NFX1 gene as well as microRNA miR-190b in the blood as compared to obese patients without signs of insulin resistance.Conclusions. Results of this study provide evidence that obesity affects the expression of the subset of genes related to immune response in the blood and that development of insulin resistance in obese adolescents is associated with strong down-regulation of the expressions of HLA-DRA, HLA-DRB1, HLA-F, and HLA-G genes, which may be contribute to the development of obesity complications. It is possible that transcription factor NFX1 and miR-190b participate in downregulation of HLA-DRA gene expression in the blood of obese adolescents with insulin resistance.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Insulin resistance in obese adolescents affects the expression of genes associated with immune response

Minchenko

2019

Endocrine Regulations

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“…For the first time in the literature, Ozer Oztekin who is an author of the present study hypothesized that HLA‐G may possibly be involved in the development of GDM 18 . Thereafter, HLA‐G is shown to be associated with insulin resistance, Type 2 DM and GDM by several studies 19–21 . Previously, we have also shown an association between HLA‐G and polycystic ovarian syndrome (PCOS), which is a disease associated with insulin resistance 22 …”

Section: Introductionmentioning

confidence: 51%

Decreased serum human leukocyte antigen‐G levels are associated with gestational diabetes mellitus

Öztekin

Çabuş

Enli

2021

J of Obstet and Gynaecol

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Aim This study was designed to determine serum human leukocyte antigen‐G (HLA‐G) levels and establish whether serum HLA‐G level is related with gestational diabetes mellitus (GDM). Methods Twenty‐five GDM patients aged between 24 and 34 years and 24 healthy pregnant women aged between 22 and 33 years were included in this study. Health status of subjects was determined by medical history, physical, and obstetric examinations. Absence of family history for Type 2 diabetes mellitus, absence of diagnosis or clinical evidence of any major disease, and absence of medication use altering glucose metabolism constituted the inclusion criteria. GDM cases who are at their 24–28 weeks of pregnancy and who have not been using any oral hypoglycemic agents were included in GDM group. Control group consisted of healthy pregnant women at their 24–28 weeks of pregnancy. Results Women with GDM had significantly lower levels of serum HLA‐G than controls. HLA‐G levels were negatively correlated with all parameters of glucose metabolism including insulin (r = − 0.14; p = 0.338), fasting blood glucose (r = − 0.220; p = 0.129), 1‐h oral glucose tolerance test (OGTT) blood glucose (r = − 0.18; p = 0.271), 2‐h OGTT blood glucose (r = − 0.314; p = 0.172), homeostasis model assessment (r = − 0.226; p = 0.119), HbA1C (r = −0.342; p = 0.108), and WBC (r = −0.149; p = 0.307). There was a negative correlation between HLA‐G and BMI (r = −0.341; p = 0.016). Conclusion Decreased circulating HLA‐G level is found to be associated with insulin resistance and GDM, in this study.

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“…In inflammatory myopathy, CD8 T cells destroy non-necrotic muscle fibers, showing a response mediated by HLA class I restricted cytotoxic T cells against surface antigens expressed in muscle fibers. Marzuillo et al [ 30 ] reported that muscle fibers, in an inflamed environment, co-express HLA-G, raising the intriguing possibility that HLA-G protects muscle fibers from injury mediated by NK cells [ 31 , 32 ]. Locally accumulated inflammatory cells produce a multitude of pro-inflammatory cytokines, including TNF-alpha and IFN-gamma.…”

Section: Discussionmentioning

confidence: 99%

High plasma soluble levels of the immune checkpoint HLA-G molecule among bodybuilders

et al. 2020

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Association between 14 bp insertion/deletion HLA‐G functional polymorphism and insulin resistance in a cohort of Italian children with obesity

Abstract: We showed a strong association between HLA-G 14 bp ins/ins genotype and HOMA in obese children and adolescents. This association could be hypothetically modulated by subclinical inflammation.

Cited by 8 publications

References 19 publications

Insulin resistance in obese adolescents affects the expression of genes associated with immune response

Insulin resistance in obese adolescents affects the expression of genes associated with immune response

Decreased serum human leukocyte antigen‐G levels are associated with gestational diabetes mellitus

High plasma soluble levels of the immune checkpoint HLA-G molecule among bodybuilders

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