Novel polymorphisms in the 5' region of the LEP gene: association with leptin levels and response to low-calorie diet in human obesity.

Mammes, Olivier; Betoulle, D; Aubert, Roberte; Giraud, V; Tuzet, S; Petiet, Alexandra; Colas-Linhart, N.; Fumeron, Frédéric

doi:10.2337/diabetes.47.3.487

Cited by 151 publications

(114 citation statements)

References 0 publications

Supporting

Mentioning

101

Contrasting

Unclassified

Order By: Relevance

“…Using LEP 19GG as the referent group, the recalculated FL risk estimate for the LEP 19AA genotype is 0.6 (95% CI 0.3 -1.3), similar to the OR of 0.5 (95% CI 0.3 -0.8) presented here. As has been observed elsewhere, the BMIs of our controls were not correlated with LEP 19G4A (r ¼ 0.014, P ¼ 0.70) (Karvonen et al, 1998;Lucantoni et al, 2000), LEP À2548G4A (r ¼ À0.013, P ¼ 0.72) (Mammes et al, 1998;Le Stunff et al, 2000), LEPR 223Q4R (r ¼ À0.008, P ¼ 0.83) (Gotoda et al, 1997;Rosmond et al, 2000;Wauters et al, 2001) or APM1 276G4T (r ¼ À0.024, P ¼ 0.51) (Menzaghi et al, 2002;Fumeron et al, 2004). Moreover, this and the previous report by Skibola et al found little evidence that risks associated with BMI varied by genotype.…”

Section: Discussionsupporting

confidence: 74%

“…However, while positive associations have been reported between NHL and anthropometric characteristics (Holly et al, 1999;Calle et al, 2003;Bahl et al, 2004;Pan et al, 2004), others have not (Paffenbarger Jr et al, 1978;Whittemore et al, 1985;Franceschi et al, 1989;La Vecchia et al, 1990;Zhang et al, 1999;Cerhan et al, 2002;Chang et al, 2005). Furthermore, polymorphisms in the LEP (an A to G nucleotide (nt) change at position 19 in the 5 0 -untranslated region (Hager et al, 1998), and a G to A substitution at nt À2548 upstream of the ATG start site (Mammes et al, 1998)) and LEPR (an A to G transition at nt 668 from the start codon that converts glutamine to arginine at codon 223 (223Q4R) (Gotoda et al, 1997)) genes were recently shown to modulate NHL risk (Skibola et al, 2004).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

et al. 2005

View full text Add to dashboard Cite

A population-based case -control study of lymphomas in England collected height and weight details from 699 non-Hodgkin's lymphoma (NHL) cases and 914 controls. Obesity, defined as a body mass index (BMI) over 30 kg m À2 at five years before diagnosis,, was associated with an increased risk of NHL (OR ¼ 1.5, 95% CI 1.1 -2.1). The excess was most pronounced for diffuse large B-cell lymphoma (OR ¼ 1.9, 95% CI 1.3 -2.8). Genetic variants in the leptin (LEP 19G4A, LEP À2548G4A) and leptin receptor genes (LEPR 223Q4R), previously shown to modulate NHL risk, as well as a polymorphism in the energy regulatory gene adiponectin (APM1 276G4T), were investigated. Findings varied with leptin genotype, the risks being decreased with LEP 19AA (OR ¼ 0.7, 95% CI 0.5 -1.0) and increased with LEP À2548GA (OR ¼ 1.3, 95% CI 1.0 -1.7) and À2548AA (OR ¼ 1.4, 95% CI 1.0 -1.9), particularly for follicular lymphoma. These genetic findings, which were independent of BMI, were stronger for men than women.

show abstract

Section: Discussionsupporting

confidence: 74%

mentioning

confidence: 99%

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

et al. 2005

View full text Add to dashboard Cite

show abstract

“…152,153 In the 5 0 region, GÀ2548A has been associated with response to low calorie diet, obesity and leptin levels. [153][154][155][156][157] Furthermore, a leptin gene 3 0 -tetranucleotide repeat is associated with BMI. 158 Finally, in the most extensive study of leptin gene polymorphisms in common obesity, common variants further upstream in the 5 0 region have displayed association with BMI.…”

Section: Pathways Controlling Lipid Storage In Adipocytesmentioning

confidence: 99%

Obesity and polymorphisms in genes regulating human adipose tissue

Dahlman

Arner

2007

Int J Obes

View full text Add to dashboard Cite

Obesity is the result of an imbalance between food intake and energy expenditure resulting in the storing of energy as fat. Adipose tissue contains the largest store of energy in the body and plays important roles in regulating energy partitioning. Developments in genomics, in particular microarray-based expression profiling, have provided scientists with a number of new candidate genes whose expression in adipose tissue is regulated by obesity. Integrating expression profiles with genome-wide linkage and/or association analyses is a promising strategy to identify new genes underlying susceptibility to obesity. This article provides a comprehensive review of adipose-tissue-expressed genes implicated in predisposition to human obesity. The authors consider the following genes of particular interest: peroxisome proliferator-activated receptor gamma and, potentially, INSIG2 acting in adipogenesis; the adrenoreceptors beta 2 and 3, as well as hormone-sensitive lipase acting on lipolysis; uncoupling protein 2 acting in mitochondria energy expenditure; and among secreted molecules the cytokine tumor necrosis factor alpha and the hormone leptin. With the rapid development in genome research, we predict that additional alleles in genes regulating adipose tissue function will be established as risk factors for common obesity in the coming years. This has important implications for the prevention of obesity and may also offer new therapeutic targets.

show abstract

mentioning

confidence: 99%

“…[15][16][17] In particular, studies of Mammes et al using DNA from peripheral blood cells documented that the Lep-2548G/A polymorphism was associated with higher leptin levels independent of BMI, before and after diet. 15 In addition, male, but not female, subjects with the Lep-2548A/A genotype had higher leptin concentrations adjusted for fat mass. 16 Similar studies suggested that nonobese women with Lep-2548A/A had higher serum leptin levels adjusted for body mass index, and significantly higher adipose tissue leptin mRNA expression than did carriers of the wildtype Lep-2548G/G sequence.…”

mentioning

confidence: 99%

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Terrasi

Fiorio

Mercanti

et al. 2009

Intl Journal of Cancer

View full text Add to dashboard Cite

Leptin is overexpressed in human breast tumors and is produced by breast cancer cells in response to obesity‐related stimuli. The leptin promoter polymorphism Lep‐2548G/A can be associated with increased leptin secretion by adipocytes and elevated cancer risk. However, molecular mechanisms underlying the link between Lep‐2548G/A and breast cancer have never been addressed. Lep‐2548G/A is proximal to a binding site for the transcriptional factor Sp1. Furthermore nucleolin, a transcriptional repressor, can bind Sp1 or its consensus site. Consequently, we focused on the impact of Lep‐2548G/A on Sp1‐ and nucleolin‐dependent leptin transcription in breast cancer cells. The Lep‐2548G/A was identified in a homozygous conformation in BT‐474 and SK‐BR‐3 breast cancer cells, in a heterozygous conformation in MDA‐MB‐231 cells, and a wild‐type Lep‐2548G/G sequence was present in MCF‐7 and ZR‐75‐1 cells. The occurrence of Lep‐2548A/A and Lep‐2548G/A coincided with high and intermediate leptin mRNA expression, respectively, while cells containing Lep‐2548G/G expressed low leptin mRNA levels. We demonstrated that the existence of Lep‐2548G/A improved efficient recruitment of Sp1 to DNA under insulin treatment, while Sp1 loading on DNA containing Lep‐2548G/G was not insulin‐dependent. In contrast, nucleolin binding to Lep‐2548G/A was downregulated in response to insulin, while it was not regulated on Lep‐2548G/G. The presence of Lep‐2548G/A was studied in breast cancer epithelial cells by IHC and LCM. Interestingly, all 14 tumors expressing high leptin levels contained Lep‐2548A/A. In conclusion, the occurrence of Lep‐2548G/A can enhance leptin expression in breast cancer cells via Sp1‐ and nucleolin‐dependent mechanisms and possibly contribute to intratumoral leptin overexpression. © 2009 UICC

show abstract

Novel polymorphisms in the 5' region of the LEP gene: association with leptin levels and response to low-calorie diet in human obesity.

Cited by 151 publications

References 0 publications

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

Non-Hodgkin's lymphoma, obesity and energy homeostasis polymorphisms

Obesity and polymorphisms in genes regulating human adipose tissue

Functional analysis of the ‐2548G/A leptin gene polymorphism in breast cancer cells

Contact Info

Product

Resources

About