LEPR p.Q223R Polymorphism Influences Plasma Leptin Levels and Body Mass Index in Tunisian Obese Patients

Ali, Samir Ben; Kallel, Amani; Sediri, Yousra; Ftouhi, B.; Feki, Moncef; Slimène, H.; Jemaa, Riadh; Kaabachi, Naziha

doi:10.1016/j.arcmed.2009.02.008

Cited by 33 publications

(27 citation statements)

References 29 publications

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“…Furthermore, in agreement with other studies [19], [33], no differences in leptin levels between the genotype groups were found, although controversial findings does exist [15], [34], [35]. It should be noted, however, that in many published studies, interpretation of the results is limited due to small sample size, differences in ethnicity of the subjects, and other factors related to the study settings.…”

Section: Discussionsupporting

confidence: 90%

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits

et al. 2012

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PurposePoor physical fitness and obesity are risk factors for all cause morbidity and mortality. We aimed to clarify whether common genetic variants of key energy intake determinants in leptin (LEP), leptin receptor (LEPR), and fat mass and obesity-associated (FTO) are associated with aerobic and neuromuscular performance, and whether aerobic fitness can alter the effect of these genotypes on body composition.Methods846 healthy Finnish males of Caucasian origin were genotyped for FTO (rs8050136), LEP (rs7799039) and LEPR (rs8179183 and rs1137101) single nucleotide polymorphisms (SNPs), and studied for associations with maximal oxygen consumption, body fat percent, serum leptin levels, waist circumference and maximal force of leg extensor muscles.ResultsGenotype AA of the FTO SNP rs8050136 associated with higher BMI and greater waist circumference compared to the genotype CC. In general linear model, no significant interaction for FTO genotype-relative VO2max (mL·kg−1·min−1) or FTO genotype-absolute VO2max (L·min−1) on BMI or waist circumference was found. Main effects of aerobic performance on body composition traits were significant (p<0.001). Logistic regression modelling found no significant interaction between aerobic fitness and FTO genotype. LEP SNP rs7799039, LEPR SNPs rs8179183 and rs1137101 did not associate with any of the measured variables, and no significant interactions of LEP or LEPR genotype with aerobic fitness were observed. In addition, none of the studied SNPs associated with aerobic or neuromuscular performance.ConclusionsAerobic fitness may not modify the effect of FTO variation on body composition traits. However, relative aerobic capacity associates with lower BMI and waist circumference regardless of the FTO genotype. FTO, LEP and LEPR genotypes unlikely associate with physical performance.

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Section: Discussionsupporting

confidence: 90%

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits

et al. 2012

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“…One study reports an increased risk for 223R for high BMI in Caucasian girls but not in boys [49]. The other study reports a protective effect of 223R in Caucasian men but not in women [50]. These results suggest that stratification by sex should be recommended for future association studies.The three SNPs of the CoLaus data showing a significant interaction with sex are all non-coding variants of the LEPR gene, as is often the case for genetic associations using high-throughput DNA chips.…”

Section: Discussionmentioning

confidence: 89%

Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight: A Systematic Review and an Analysis of the CoLaus Study

et al. 2011

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BackgroundThree non-synonymous single nucleotide polymorphisms (Q223R, K109R and K656N) of the leptin receptor gene (LEPR) have been tested for association with obesity-related outcomes in multiple studies, showing inconclusive results. We performed a systematic review and meta-analysis on the association of the three LEPR variants with BMI. In addition, we analysed 15 SNPs within the LEPR gene in the CoLaus study, assessing the interaction of the variants with sex.Methodology/Principal FindingsWe searched electronic databases, including population-based studies that investigated the association between LEPR variants Q223R, K109R and K656N and obesity- related phenotypes in healthy, unrelated subjects. We furthermore performed meta-analyses of the genotype and allele frequencies in case-control studies. Results were stratified by SNP and by potential effect modifiers. CoLaus data were analysed by logistic and linear regressions and tested for interaction with sex. The meta-analysis of published data did not show an overall association between any of the tested LEPR variants and overweight. However, the choice of a BMI cut-off value to distinguish cases from controls was crucial to explain heterogeneity in Q223R. Differences in allele frequencies across ethnic groups are compatible with natural selection of derived alleles in Q223R and K109R and of the ancient allele in K656N in Asians. In CoLaus, the rs10128072, rs3790438 and rs3790437 variants showed interaction with sex for their association with overweight, waist circumference and fat mass in linear regressions.ConclusionsOur systematic review and analysis of primary data from the CoLaus study did not show an overall association between LEPR SNPs and overweight. Most studies were underpowered to detect small effect sizes. A potential effect modification by sex, population stratification, as well as the role of natural selection should be addressed in future genetic association studies.

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“…A series of experiments showed that the Q223R polymorphism did not affect transcription in mouse models or leptin receptor activity in vitro [64], which conflicts with previously reported associations between Q223R and circulating leptin levels [59, 65, 66]. Further research is necessary to confirm whether these candidate SNPs have functional effects or are markers for other causal genetic variants.…”

Section: Discussionmentioning

confidence: 93%

Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

Nyante

Gammon

Kaufman

et al. 2011

Breast Cancer Res Treat

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Adipocytokines are produced by visceral fat, and levels may be associated with breast cancer risk. We investigated whether single nucleotide polymorphisms (SNPs) in adipocytokine genes adiponectin (ADIPOQ), leptin (LEP), and the leptin receptor (LEPR) were associated with basal-like or luminal A breast cancer subtypes. 104 candidate and tag SNPs were genotyped in 1776 of 2022 controls and 1972 (200 basal-like, 679 luminal A) of 2311 cases from the Carolina Breast Cancer Study (CBCS), a population-based case–control study of whites and African Americans. Breast cancer molecular subtypes were determined by immunohistochemistry. Genotype odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression. Haplotype ORs and 95% CIs were estimated using Hapstat. Interactions with waist-hip ratio were evaluated using a multiplicative interaction term. Ancestry was estimated from 144 ancestry informative markers (AIMs), and included in models to control for population stratification. Candidate SNPs LEPR K109R (rs1137100) and LEPR Q223R (rs1137101) were positively associated with luminal A breast cancer, whereas ADIPOQ +45 T/G (rs2241766), ADIPOQ +276 G/T (rs1501299), and LEPR K656N (rs8129183) were not associated with either subtype. Few patterns were observed among tag SNPs, with the exception of 3 LEPR SNPs (rs17412175, rs9436746, and rs9436748) that were in moderate LD and inversely associated with basal-like breast cancer. However, no SNP associations were statistically significant after adjustment for multiple comparisons. Haplotypes in LEP and LEPR were associated with both basal-like and luminal A subtypes. There was no evidence of interaction with waist-hip ratio. Data suggest associations between LEPR candidate SNPs and luminal A breast cancer in the CBCS and LEPR intron 2 tag SNPs and basal-like breast cancer. Replication in additional studies where breast cancer subtypes have been defined is necessary to confirm these potential associations.

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LEPR p.Q223R Polymorphism Influences Plasma Leptin Levels and Body Mass Index in Tunisian Obese Patients

Cited by 33 publications

References 29 publications

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits

Aerobic Fitness Does Not Modify the Effect of FTO Variation on Body Composition Traits

Association between Variants of the Leptin Receptor Gene (LEPR) and Overweight: A Systematic Review and an Analysis of the CoLaus Study

Common genetic variation in adiponectin, leptin, and leptin receptor and association with breast cancer subtypes

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