Dataset Information

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

ABSTRACT:

Introduction

Leptin is a hormone secreted from adipocytes that regulates metabolism and energy homeostasis through the leptin receptor (LEPR). The aim of this study was to investigate the association of leptin receptor gene Q223R gene polymorphism, and plasma leptin level among obese breast cancer females.

Materials and methods

The study enrolled 160 breast cancer patients and 160 healthy control females. LEPR Q223R polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Serum leptin was determined using enzyme-linked immunosorbent assay human leptin kit. Immunohistochemical tests from paraffin blocks were carried out for estrogen and progesterone staging using the precise antibodies.

Results

An association was found between LEPR gene Q223R gene polymorphism among obese breast cancer females. Statistical difference was found between GG (60.6%) Arg/Arg genotype (OR=2.986; 95%CI=1.540 to 5.789; p= 0.001) compared to AA (33.1%) Gln/Gln genotype. GG Q223R LEPR polymorphism showed statistically significant difference among obese breast cancer patients (BMI more than 25) compared to control (P < 0.0001). GG genotype of Q223R LEPR polymorphism showed statistically significant increased leptin level (p-value =0.0001) among obese patients (mean± SD; 23.39±4.32) compared to control (17.83±5.67).

Conclusions

Q223R LEPR polymorphism GG genotype was associated with increased leptin profile among obese breast cancer females.

SUBMITTER: Atoum MF

PROVIDER: S-EPMC9258657 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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Publications

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

Atoum Manar F MF Hamaid Alparrey Ala'a Abdel AA

Asian Pacific journal of cancer prevention : APJCP 20220101 1

<h4>Introduction</h4>Leptin is a hormone secreted from adipocytes that regulates metabolism and energy homeostasis through the leptin receptor (LEPR). The aim of this study was to investigate the association of leptin receptor gene Q223R gene polymorphism, and plasma leptin level among obese breast cancer females.<h4>Materials and methods</h4>The study enrolled 160 breast cancer patients and 160 healthy control females. LEPR Q223R polymorphism was determined by polymerase chain reaction-restrict ...[more]

PMID: 35092386

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Project description:Obesity is associated with breast cancer in post-menopausal women, and breast density is a marker of breast cancer risk. Leptin is produced by the adipose tissue, acts through receptors that are polymorphic in nature, and is considered a cancer growth factor. The relationship between body mass index, leptin, leptin receptors and breast density is not well studied. A cross-sectional analysis in 392 post-menopausal healthy women was conducted; participants provided permission to obtain copies of their most recent screening mammogram. Non-fasting plasma leptin levels were determined using a commercially available leptin ELISA kit. Analysis of the Q223R genotypes of the LEPR gene were performed by PCR followed by restriction fragment length polymorphism analysis using DNA extracted from buffy coat samples. A statistically significant positive relationship was observed between leptin levels and body mass index (p<0.0001); leptin was significantly positively associated with mammography total breast area and non-dense breast area (p<0.0001), while it was inversely associated with percent breast density (p<0.0001). Leptin levels varied across the LEPR Q223R polymorphism, and were higher in women homozygous for the AA variant. Percent breast density decreased across the LEPR Q223R genotype, with lower percent density in women with the AA genotype. When dense area was considered according to quartiles of leptin and stratified by LEPR Q223R, a significant inverse trend between leptin levels and dense breast area was observed only among women with the G/G genotype (p-trend<0.001). After adjustment for possible confounders, leptin levels were significantly inversely associated with percent breast density (p=0.01). A significant interaction between body mass index and leptin levels on percent breast density was observed (p=0.03). These findings suggest that the association between leptin and breast density may vary by LEPR Q223R genotype, and that body mass index and leptin may act in an interactive way in determining breast density.

Project description:Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity. Resistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues analyzed for changes in gene expression. By 72 h post-challenge all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. 37 genes were differentially expressed in response to infection at 72 h, including pro-inflammatory genes (CXCL2, calprotectin (S100A8/9), Pla2g7, Itbg2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h post-challenge of infected Q223 vs. R223 mice identified a subset of differentially-expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide to this previously uncharacterized mechanism of mucosal immunity.

Project description:Leptin is a key hormone of weight regulation that modulates food intake. Since the elaboration of the leptin action mechanism, several studies tried to establish the relationship between obesity and the common polymorphisms of leptin (LEP) and leptin receptor (LEPR) genes, but results were controversial. We studied the association of G2548A of the LEP gene and Q223R of LEPR gene polymorphisms with obesity and metabolic syndrome (MetS). We recruited 169 nonobese volunteers (body mass index [BMI] < 30 kg/m(2)) and 160 obese ones (BMI ≥ 30 kg/m(2)). Glucose, insulin, and lipids were measured. BMI, homeostasis model assessment-insulin resistance (HOMA-IR), and daily energy intake were calculated. After adjustment to confounders parameters, 2548AA was found to increase the MetS (p=0.043) and obesity risk (p=0.019) in the studied population. After stratification according to the degree of obesity, the odds ratio [OR] of 2548AA was associated with moderate obesity (p=0.048) and morbid obesity (p=0.048). The LEPR 223RR genotype was associated with obesity in the studied population (OR=1.74, p=0.037) and only in the overweight (OR=1.8, p=0.049). Subjects with 2548AA had significantly higher BMI, daily energy intake, total cholesterol (TC), waist circumference (WC), insulinemia, and low high-density lipoprotein-cholesterol (HDL-C) levels. With regard to 223RR, we noted a significantly higher daily energy intake, BMI, TC, glycemia, insulinemia, HOMA-IR index, and low HDL-C levels. Haplotype model AR (2548A+223R) and AQ (2548A+223Q) increased the risk of obesity (OR=3.36, p<0.001; OR=2.56, p=0.010, respectively). When we added daily energy intake in adjustment, these significant associations disappeared. In addition, the AR and AQ increased the MetS risk. This significant association persisted after we had added daily energy intake in adjustment. This study showed that LEP G2548A and LEPR Q223R polymorphisms and haplotype combination were associated with MetS and obesity risk in Tunisian volunteers.

Dataset Information

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

Introduction

Materials and methods

Results

Conclusions

Publications

Association of Leptin Receptor Q223R Gene Polymorphism and Breast Cancer Patients: A Case Control Study.

Similar Datasets

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