Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels

Yuan Yuan Zhang, Lucia Gottardo, Wojciech Mlynarski, Winfred Frazier, David Nolan, Jill Duffy, Maria Cristina Marescotti, Ernest V. Gervino, Michael T. Johnstone, Christos S. Mantzoros, Angelo Avogaro, Alessandro Doria

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Objective: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP-two markers of inflammation and susceptibility to atherosclerosis. Methods and results: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p = 0.005), accounting for 3% of its variance (r2 = 0.030). The same block was also associated with CRP levels (p = 0.049, r2 = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p = 0.015). At rs1805096, it was 5% higher (p = 0.007) and CRP 32% higher (p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Conclusions: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.

Original languageEnglish (US)
Pages (from-to)121-127
Number of pages7
JournalAtherosclerosis
Volume191
Issue number1
DOIs
StatePublished - Mar 2007
Externally publishedYes

Fingerprint

Leptin Receptors
C-Reactive Protein
Fibrinogen
Homozygote
Alleles
Single Nucleotide Polymorphism
Atherosclerosis
Leptin
Haplotypes
Linkage Disequilibrium
Heterozygote
Inflammation

Keywords

  • CRP
  • Fibrinogen
  • Genetics
  • Inflammation
  • Leptin

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels. / Zhang, Yuan Yuan; Gottardo, Lucia; Mlynarski, Wojciech; Frazier, Winfred; Nolan, David; Duffy, Jill; Marescotti, Maria Cristina; Gervino, Ernest V.; Johnstone, Michael T.; Mantzoros, Christos S.; Avogaro, Angelo; Doria, Alessandro.

In: Atherosclerosis, Vol. 191, No. 1, 03.2007, p. 121-127.

Research output: Contribution to journalArticle

Zhang, YY, Gottardo, L, Mlynarski, W, Frazier, W, Nolan, D, Duffy, J, Marescotti, MC, Gervino, EV, Johnstone, MT, Mantzoros, CS, Avogaro, A & Doria, A 2007, 'Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels', Atherosclerosis, vol. 191, no. 1, pp. 121-127. https://doi.org/10.1016/j.atherosclerosis.2006.02.043
Zhang, Yuan Yuan ; Gottardo, Lucia ; Mlynarski, Wojciech ; Frazier, Winfred ; Nolan, David ; Duffy, Jill ; Marescotti, Maria Cristina ; Gervino, Ernest V. ; Johnstone, Michael T. ; Mantzoros, Christos S. ; Avogaro, Angelo ; Doria, Alessandro. / Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels. In: Atherosclerosis. 2007 ; Vol. 191, No. 1. pp. 121-127.
@article{80bd0542c7ab464589a5d5a5508c7dc0,
title = "Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels",
abstract = "Objective: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP-two markers of inflammation and susceptibility to atherosclerosis. Methods and results: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p = 0.005), accounting for 3{\%} of its variance (r2 = 0.030). The same block was also associated with CRP levels (p = 0.049, r2 = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10{\%} higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p = 0.015). At rs1805096, it was 5{\%} higher (p = 0.007) and CRP 32{\%} higher (p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Conclusions: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.",
keywords = "CRP, Fibrinogen, Genetics, Inflammation, Leptin",
author = "Zhang, {Yuan Yuan} and Lucia Gottardo and Wojciech Mlynarski and Winfred Frazier and David Nolan and Jill Duffy and Marescotti, {Maria Cristina} and Gervino, {Ernest V.} and Johnstone, {Michael T.} and Mantzoros, {Christos S.} and Angelo Avogaro and Alessandro Doria",
year = "2007",
month = "3",
doi = "10.1016/j.atherosclerosis.2006.02.043",
language = "English (US)",
volume = "191",
pages = "121--127",
journal = "Atherosclerosis",
issn = "0021-9150",
publisher = "Elsevier Ireland Ltd",
number = "1",

}

TY - JOUR

T1 - Genetic variability at the leptin receptor (LEPR) locus is a determinant of plasma fibrinogen and C-reactive protein levels

AU - Zhang, Yuan Yuan

AU - Gottardo, Lucia

AU - Mlynarski, Wojciech

AU - Frazier, Winfred

AU - Nolan, David

AU - Duffy, Jill

AU - Marescotti, Maria Cristina

AU - Gervino, Ernest V.

AU - Johnstone, Michael T.

AU - Mantzoros, Christos S.

AU - Avogaro, Angelo

AU - Doria, Alessandro

PY - 2007/3

Y1 - 2007/3

N2 - Objective: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP-two markers of inflammation and susceptibility to atherosclerosis. Methods and results: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p = 0.005), accounting for 3% of its variance (r2 = 0.030). The same block was also associated with CRP levels (p = 0.049, r2 = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p = 0.015). At rs1805096, it was 5% higher (p = 0.007) and CRP 32% higher (p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Conclusions: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.

AB - Objective: Cellular and animal studies suggest that leptin has proinflammatory and prothrombotic effects that could link increased adipose mass directly to atherogenesis. To investigate this hypothesis, we examined the effect of genetic variability at the leptin receptor (LEPR) locus on the plasma levels of fibrinogen and CRP-two markers of inflammation and susceptibility to atherosclerosis. Methods and results: Linkage disequilibrium analysis of 71 single-nucleotide polymorphisms (SNPs) spanning the LEPR locus revealed four haplotype blocks that could be tagged by 11 SNPs. In 630 healthy Caucasian individuals, variability in block #4 was significantly associated with plasma fibrinogen (p = 0.005), accounting for 3% of its variance (r2 = 0.030). The same block was also associated with CRP levels (p = 0.049, r2 = 0.022). The effect was strongest for two of the SNPs in this block. At rs3790432, fibrinogen was 10% higher in minor allele homozygotes than in major allele homozygotes and intermediate in heterozygotes (p = 0.015). At rs1805096, it was 5% higher (p = 0.007) and CRP 32% higher (p = 0.011) in major allele homozygotes than in minor allele carriers. This pattern of association was also evident in the haplotype analysis. Conclusions: Association of leptin receptor variability with inflammatory traits supports the hypothesis that leptin may play a role in atherogenesis.

KW - CRP

KW - Fibrinogen

KW - Genetics

KW - Inflammation

KW - Leptin

UR - http://www.scopus.com/inward/record.url?scp=33846910244&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846910244&partnerID=8YFLogxK

U2 - 10.1016/j.atherosclerosis.2006.02.043

DO - 10.1016/j.atherosclerosis.2006.02.043

M3 - Article

VL - 191

SP - 121

EP - 127

JO - Atherosclerosis

JF - Atherosclerosis

SN - 0021-9150

IS - 1

ER -