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Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans.

ABSTRACT: OBJECTIVE:The role of genetic factors in the development of obesity is largely unreported in Sri Lankans. The Q223R (rs1137101) single nucleotide polymorphism (SNP) of the leptin receptor (LEPR) gene has been associated with obesity measures in various ethnicities. We investigated the association of the Q223R polymorphism with obesity related anthropometric measures and biochemical parameters fasting blood glucose and lipid profile in a sample of 530 Sri Lankan adult subjects (age 18-70 years) representing both urban and rural areas of residence. RESULTS:The LEPR Q223R variant G allele frequency was 0.54. The polymorphism was associated with body mass index (p?=?0.04) and waist circumference (p?=?0.02) measures in overweight and obese (BMI???25 kgm-2) subjects with the variant allele conferring a greater risk of adiposity. Residency in urban areas eliminated the protective effect of the non-risk genotype (AA) in the development of obesity.

SUBMITTER: Illangasekera YA

PROVIDER: S-EPMC6966896 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans.

Illangasekera Y A YA Kumarasiri P V R PVR Fernando D J DJ Dalton C F CF

BMC research notes 20200116 1

<h4>Objective</h4>The role of genetic factors in the development of obesity is largely unreported in Sri Lankans. The Q223R (rs1137101) single nucleotide polymorphism (SNP) of the leptin receptor (LEPR) gene has been associated with obesity measures in various ethnicities. We investigated the association of the Q223R polymorphism with obesity related anthropometric measures and biochemical parameters fasting blood glucose and lipid profile in a sample of 530 Sri Lankan adult subjects (age 18-70 ...[more]

PMID: 31948470

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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.

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.

Dataset Information

Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans.

Publications

Association of the leptin receptor Q223R (rs1137101) polymorphism with obesity measures in Sri Lankans.

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