Leptin signaling and hyperparathyroidism: Clinical and genetic associations

Don Hoang, Niclas Broer, Sanziana A. Roman, Xiaopan Yao, Nathalie Abitbol, Fangyong Li, Julie A. Sosa, Gloria R. Sue, Andrew T. Dewan, Ma Li Wong, Julio Licinio, Christine Simpson, Alexander Y. Li, Nicole Pizzoferrato, Deepak Narayan

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Background The role of leptin in mediating calcium-related metabolic processes is not well understood. Study Design We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism. Results Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively). Conclusions Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.

LanguageEnglish
Pages1239-1250.e4
JournalJournal of the American College of Surgeons
Volume218
Issue number6
DOIs
Publication statusPublished - 1 Jan 2014

ASJC Scopus subject areas

  • Surgery

Cite this

Hoang, D., Broer, N., Roman, S. A., Yao, X., Abitbol, N., Li, F., ... Narayan, D. (2014). Leptin signaling and hyperparathyroidism: Clinical and genetic associations. Journal of the American College of Surgeons, 218(6), 1239-1250.e4. https://doi.org/10.1016/j.jamcollsurg.2013.11.013
Hoang, Don ; Broer, Niclas ; Roman, Sanziana A. ; Yao, Xiaopan ; Abitbol, Nathalie ; Li, Fangyong ; Sosa, Julie A. ; Sue, Gloria R. ; Dewan, Andrew T. ; Wong, Ma Li ; Licinio, Julio ; Simpson, Christine ; Li, Alexander Y. ; Pizzoferrato, Nicole ; Narayan, Deepak. / Leptin signaling and hyperparathyroidism : Clinical and genetic associations. In: Journal of the American College of Surgeons. 2014 ; Vol. 218, No. 6. pp. 1239-1250.e4.
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title = "Leptin signaling and hyperparathyroidism: Clinical and genetic associations",
abstract = "Background The role of leptin in mediating calcium-related metabolic processes is not well understood. Study Design We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism. Results Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively). Conclusions Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.",
author = "Don Hoang and Niclas Broer and Roman, {Sanziana A.} and Xiaopan Yao and Nathalie Abitbol and Fangyong Li and Sosa, {Julie A.} and Sue, {Gloria R.} and Dewan, {Andrew T.} and Wong, {Ma Li} and Julio Licinio and Christine Simpson and Li, {Alexander Y.} and Nicole Pizzoferrato and Deepak Narayan",
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Hoang, D, Broer, N, Roman, SA, Yao, X, Abitbol, N, Li, F, Sosa, JA, Sue, GR, Dewan, AT, Wong, ML, Licinio, J, Simpson, C, Li, AY, Pizzoferrato, N & Narayan, D 2014, 'Leptin signaling and hyperparathyroidism: Clinical and genetic associations', Journal of the American College of Surgeons, vol. 218, no. 6, pp. 1239-1250.e4. https://doi.org/10.1016/j.jamcollsurg.2013.11.013

Leptin signaling and hyperparathyroidism : Clinical and genetic associations. / Hoang, Don; Broer, Niclas; Roman, Sanziana A.; Yao, Xiaopan; Abitbol, Nathalie; Li, Fangyong; Sosa, Julie A.; Sue, Gloria R.; Dewan, Andrew T.; Wong, Ma Li; Licinio, Julio; Simpson, Christine; Li, Alexander Y.; Pizzoferrato, Nicole; Narayan, Deepak.

In: Journal of the American College of Surgeons, Vol. 218, No. 6, 01.01.2014, p. 1239-1250.e4.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Leptin signaling and hyperparathyroidism

T2 - Journal of the American College of Surgeons

AU - Hoang, Don

AU - Broer, Niclas

AU - Roman, Sanziana A.

AU - Yao, Xiaopan

AU - Abitbol, Nathalie

AU - Li, Fangyong

AU - Sosa, Julie A.

AU - Sue, Gloria R.

AU - Dewan, Andrew T.

AU - Wong, Ma Li

AU - Licinio, Julio

AU - Simpson, Christine

AU - Li, Alexander Y.

AU - Pizzoferrato, Nicole

AU - Narayan, Deepak

PY - 2014/1/1

Y1 - 2014/1/1

N2 - Background The role of leptin in mediating calcium-related metabolic processes is not well understood. Study Design We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism. Results Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively). Conclusions Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.

AB - Background The role of leptin in mediating calcium-related metabolic processes is not well understood. Study Design We enrolled patients with hyperparathyroidism undergoing parathyroidectomy in a prospective study to assess postoperative changes to serum leptin and parathyroid hormone levels and to determine the presence of LEPR (leptin receptor) polymorphisms. Patients undergoing hemithyroidectomy under identical surgical conditions were enrolled as controls. Wilcoxon signed-rank test was used to analyze changes in leptin. Pearson correlations and Bland-Altman methods were used to examine the between-subject and within-subject correlations in changes in leptin and parathyroid hormone levels. Five single-nucleotide polymorphisms in the LEPR gene were genotyped, and linear regression analysis was performed for each polymorphism. Results Among the 71 patients included in the clinical study, after-surgery leptin levels decreased significantly in the parathyroid adenoma (p < 0.001) and parathyroid hyperplasia subgroups (p = 0.002) and increased in the control group (p = 0.007). On multivariate analysis, parathyroid disease subtype, baseline leptin levels, age, body mass index, and calcium at diagnosis was associated with changes in leptin. Among the 132 patients included in the genotyping analysis, under a recessive model of inheritance, single-nucleotide polymorphism rs1137101 had a significant association with the largest parathyroid gland and total mass of parathyroid tissue removed (p = 0.045 and p = 0.040, respectively). When analyzing obese patients only, rs1137100 and rs1137101 were significantly associated with total parathyroid size (p = 0.0343 and p = 0.0259, respectively). Conclusions Our results suggest a role for the parathyroid gland in regulating leptin production. Genetic contributions from the leptin pathway might predispose to hyperparathyroidism.

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U2 - 10.1016/j.jamcollsurg.2013.11.013

DO - 10.1016/j.jamcollsurg.2013.11.013

M3 - Article

VL - 218

SP - 1239-1250.e4

JO - Journal of the American College of Surgeons

JF - Journal of the American College of Surgeons

SN - 1072-7515

IS - 6

ER -