Leptin Receptor Genotype at Gln223Arg is Associated With Body Composition, BMD, and Vertebral Fracture in Postmenopausal Danish Women

Fairbrother, Una; Tankó, László B.; Walley, Andrew J.; Christiansen, Claus; Froguel, Philippe; Blakemore, Alexandra I. F.

doi:10.1359/jbmr.070114

Cited by 46 publications

(21 citation statements)

References 57 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The results differ, with some studies finding an association with the substitution of adenine by guanine in position 668 of exon 6 (Gln223Arg) and changes in bone mass and an increase in vertebral fractures [11,12], but no modifications of bone density with the Lys656Asn polymorphism. These results are similar to those of our study.…”

Section: Discussioncontrasting

confidence: 58%

Atorvastatin and BMD in Coronary Syndrome. Role of Lys656Asn Polymorphism of Leptin Receptor Gene

et al. 2009

View full text Add to dashboard Cite

Abstract. Objectives. To evaluate the effect of atorvastatin on bone mass and markers of bone remodeling in patients with acute coronary syndrome according to the Lys656Asn leptin receptor gene polymorphism. Methods. Sixty-two patients with acute coronary syndrome were included. Patients were allocated to low and high doses of atorvastatin according to baseline levels of cholesterol and triglycerides and the index of vascular risk and were studied at hospital admission and at 12 months. Cholesterol, triglycerides, total calcium, phosphorus, magnesium, osteocalcin and urinary deoxypyridinoline were determined in all patients at baseline and at 12 months of follow up. Densitometric studies were conducted in the lumbar spine and hip. Patients with a T-score<-2.5 were considered osteoporotic. The Lys656Asn leptin receptor gene polymorphism was determined by PCR. Results. Forty-two patients were Lys/Lys homozygotic and 20 Lys/Asn heterozygotic. The prevalence of osteoporosis was 31% for the Lys/Lys genotype and 27% for the Lys/Asn genotype with no significant differences between groups. There was a significant increase in bone mineral density in the lumbar spine (1.117 ± 0.24 versus 1.135 ± 0.24, P = 0.008) in patients with the Lys/Lys genotype. Conclusion. Atorvastatin increases lumbar spine bone mineral density only in patients with the Lys/Lys genotype of the Lys656Asn polymorphism. . Inflammatory cytokines play an important role in the imbalance between bone formation and resorption that leads to the reduced bone mass seen in osteoporosis [3]. In addition, drugs such as statins are effective in both diseases, diminishing vascular events in patients with atherosclerosis and increasing bone mass in those with high levels of cholesterol [4]. Human leptin is a protein of 167 amino acids manufactured in fat cells which is involved in regulating the ingestion and consumption of energy. It intervenes in the regulation of bone mass by means of a central hypothalamic mechanism, exerting a double antagonistic effect on bone formation and resorption through activation of the sympathetic nervous system and the Cocaine Amphetamine Regulated Transcript (CART) [5]. In addition, studies have shown that hyperleptinemia can exert atherogenic effects [6]. In North American patients, elevated leptin levels have been associated with an increased risk of myocardial infarction in both males (3.16, 95% CI 1.40-7.37) and females (3.95, 95% CI 1.29-12.72) [7].Leptin exerts its biological effect by bonding with a receptor from the cytokine-receptor family. The leptin

show abstract

Section: Discussioncontrasting

confidence: 58%

Atorvastatin and BMD in Coronary Syndrome. Role of Lys656Asn Polymorphism of Leptin Receptor Gene

et al. 2009

View full text Add to dashboard Cite

show abstract

“…In literature, both alleles of these SNPs have been reported as risk alleles for type 2 diabetes and obesity, and a metaanalytic study reported nonsignificant associations. [23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39]48 Consequently, additional studies in larger populations need to be carried out, to verify the involvement of these coding LEPR SNPs in the 'fetal insulin hypothesis'.…”

Section: Discussionmentioning

confidence: 99%

“…In this study we therefore examined the effect of common SNPs in LEP and LEPR on birth weight and adult metabolic risk factors for type 2 diabetes measured in young twins recruited from the East Flanders Prospective Twin Survey (EFPTS). The SNPs studied have previously been associated with type 2 diabetesrelated traits in other populations, [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] and are either nonsynonymous or located in a region that might be of importance in the regulation of gene expression.…”

Section: Introductionmentioning

confidence: 99%

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

et al. 2008

View full text Add to dashboard Cite

Objective: Children born small for gestational age are at increased risk of developing type 2 diabetes in adulthood. The satiety signal leptin that regulates food intake and energy expenditure might be a possible molecular link, as umbilical cord leptin levels are positively correlated with birth weight. In the present study, we examined whether common single nucleotide polymorphisms (SNPs) in the leptin (LEP; 19G4A) gene and its receptor (LEPR; Q223R and K109R) are associated with birth weight and adult metabolic risk factors for type 2 diabetes in twins. Design: SNPs were genotyped in 396 monozygotic and 232 dizygotic twins (286 men and 342 women, mean age 25 years) recruited from the East Flanders Prospective Twin Survey. Data were analysed using linear mixed models. Results: The LEPR K109R SNP was associated with birth weight (KK, KR and RR (95% confidence interval, CI): 2511 (2465-2557), 2575 (2516-2635) and 2726 (2606-2845) gram; P additive ¼ 0.001). Also the LEPR Q223R SNP showed a significant association with weight at birth (QQ, QR and RR (95% CI): 2492 (2431-2554), 2545 (2495-2595) and 2655 (2571-2740) gram; P additive ¼ 0.003). Furthermore, an interaction between the LEPR K109R and the Q223R SNP on birth weight was observed (P ¼ 0.014). G allele carriers of the LEP 19G4A SNP had higher high-density lipoprotein (HDL) cholesterol levels compared to 19A homozygotes (GX vs AA (95% CI): 1.62 (1.58-1.66) vs 1.49 (1.40-1.58) mmol l À1 ; P recessive ¼ 0.013). Conclusions: This study indicates that leptin may act as a growth-promoting signal during fetal development, and suggests a possible role for the LEPR in explaining the inverse relationship between birth weight and the development of metabolic diseases in adulthood. Additionally, these results suggest that the LEP 19G4A SNP affect HDL cholesterol levels.

show abstract

“…It was shown recently in vivo, in animals and in humans, that glucocorticoidinduced osteoporosis has been linked to leptin production. 34,35 In view of the known properties of leptin on bone metabolism, it is tempting to speculate that corticosteroid exposure, leptin production and demineralization are linked events. Accordingly, the blockade of the leptin production would be favorable.…”

Section: Discussionmentioning

confidence: 99%

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Relić

Zeddou

Desoroux

et al. 2009

Laboratory Investigation

View full text Add to dashboard Cite

It was shown recently that synovial fibroblast transformation into adipocytes reduced the expression of interleukin-6 (IL-6) and IL-8. However, the synovial fibroblast adipogenesis was inhibited in inflammatory conditions induced by the tumor necrosis factor-a (TNF-a). Furthermore, adipogenesis is often accompanied by leptin production, a proinflammatory adipokine in rheumatic diseases. In this study, we tested the phytohormone genistein for adipogenic and anti-inflammatory properties on human synovial fibroblasts. Results showed that genistein was able to transform synovial fibroblasts into adipocytes that expressed perilipin-A and produced adiponectin, but not leptin. Furthermore, genistein enhanced glucocorticoid-mediated synovial fibroblast adipogenesis and, in parallel, downregulated glucocorticoid-induced leptin and leptin receptor. Endogenous and TNF-a-induced expressions of IL-6, IL-8, p38, p65 and C/EBP-b were also downregulated by genistein, showing its anti-inflammatory properties. Peroxisome proliferatoractivated receptor-g (PPAR-g) agonist, rosiglitazone, had a synergic effect on genistein-induced adipogenesis, whereas the non-active tyrosine kinase inhibitor, daidzein, had a significantly inferior adipogenic activity than genistein. The Janus kinase-2 tyrosine kinase inhibitor, AG 490, mimicked the anti-leptin effect of genistein. These results showed that genistein-induced adipogenesis involves PPAR-g induction and tyrosine kinase inhibition. In conclusion, genistein, alone or coupled with glucocorticoids, have both adipogenic and anti-inflammatory effects on synovial fibroblasts.

show abstract

Leptin Receptor Genotype at Gln223Arg is Associated With Body Composition, BMD, and Vertebral Fracture in Postmenopausal Danish Women

Cited by 46 publications

References 57 publications

Atorvastatin and BMD in Coronary Syndrome. Role of Lys656Asn Polymorphism of Leptin Receptor Gene

Atorvastatin and BMD in Coronary Syndrome. Role of Lys656Asn Polymorphism of Leptin Receptor Gene

Common SNPs in LEP and LEPR associated with birth weight and type 2 diabetes-related metabolic risk factors in twins

Genistein induces adipogenesis but inhibits leptin induction in human synovial fibroblasts

Contact Info

Product

Resources

About