PMID- 21233811
OWN - NLM
STAT- MEDLINE
DCOM- 20110913
LR  - 20221207
IS  - 1930-739X (Electronic)
IS  - 1930-7381 (Linking)
VI  - 19
IP  - 6
DP  - 2011 Jun
TI  - Multilocus analyses of seven candidate genes suggest interacting pathways for 
      obesity-related traits in Brazilian populations.
PG  - 1244-51
LID - 10.1038/oby.2010.325 [doi]
AB  - We investigated whether variants in major candidate genes for food intake and 
      body weight regulation contribute to obesity-related traits under a multilocus 
      perspective. We studied 375 Brazilian subjects from partially isolated 
      African-derived populations (quilombos). Seven variants displaying conflicting 
      results in previous reports and supposedly implicated in the susceptibility of 
      obesity-related phenotypes were investigated: beta2-adrenergic receptor (ADRB2) 
      (Arg16Gly), insulin induced gene 2 (INSIG2) (rs7566605), leptin (LEP) (A19G), LEP 
      receptor (LEPR) (Gln223Arg), perilipin (PLIN) (6209T > C), peroxisome 
      proliferator-activated receptor-gamma (PPARG) (Pro12Ala), and resistin (RETN) (-420 C 
      > G). Regression models as well as generalized multifactor dimensionality 
      reduction (GMDR) were employed to test the contribution of individual effects and 
      higher-order interactions to BMI and waist-hip ratio (WHR) variation and risk of 
      overweight/obesity. The best multilocus association signal identified in the 
      quilombos was further examined in an independent sample of 334 Brazilian subjects 
      of European ancestry. In quilombos, only the PPARG polymorphism displayed 
      significant individual effects (WHR variation, P = 0.028). No association was 
      observed either with the risk of overweight/obesity (BMI >/= 25 kg/m2), risk of 
      obesity alone (BMI >/= 30 kg/m2) or BMI variation. However, GMDR analyses revealed 
      an interaction between the LEPR and ADRB2 polymorphisms (P = 0.009) as well as a 
      third-order effect involving the latter two variants plus INSIG2 (P = 0.034) with 
      overweight/obesity. Assessment of the LEPR-ADRB2 interaction in the second sample 
      indicated a marginally significant association (P = 0.0724), which was further 
      verified to be limited to men (P = 0.0118). Together, our findings suggest 
      evidence for a two-locus interaction between the LEPR Gln223Arg and ADRB2 
      Arg16Gly variants in the risk of overweight/obesity, and highlight further the 
      importance of multilocus effects in the genetic component of obesity.
FAU - Angeli, Claudia B
AU  - Angeli CB
AD  - Centro de Estudos do Genoma Humano, Departamento de Genetica e Biologia; 
      Evolutiva, Instituto de Biociencias, Universidade de Sao Paulo, Sao Paulo, 
      Brazil.
FAU - Kimura, Lilian
AU  - Kimura L
FAU - Auricchio, Maria T
AU  - Auricchio MT
FAU - Vicente, Joao P
AU  - Vicente JP
FAU - Mattevi, Vanessa S
AU  - Mattevi VS
FAU - Zembrzuski, Veronica M
AU  - Zembrzuski VM
FAU - Hutz, Mara H
AU  - Hutz MH
FAU - Pereira, Alexandre C
AU  - Pereira AC
FAU - Pereira, Tiago V
AU  - Pereira TV
FAU - Mingroni-Netto, Regina C
AU  - Mingroni-Netto RC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110113
PL  - United States
TA  - Obesity (Silver Spring)
JT  - Obesity (Silver Spring, Md.)
JID - 101264860
RN  - 0 (ADRB2 protein, human)
RN  - 0 (INSIG2 protein, human)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (LEPR protein, human)
RN  - 0 (Membrane Proteins)
RN  - 0 (PPAR gamma)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Receptors, Leptin)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - Body Weights and Measures
MH  - Brazil
MH  - Energy Intake
MH  - Female
MH  - Genetic Association Studies
MH  - Humans
MH  - Indians, South American
MH  - Intracellular Signaling Peptides and Proteins/genetics
MH  - Male
MH  - Membrane Proteins/genetics
MH  - Middle Aged
MH  - Multifactor Dimensionality Reduction
MH  - Multilocus Sequence Typing
MH  - Obesity/ethnology/*genetics/*physiopathology
MH  - Overweight/ethnology/genetics/physiopathology
MH  - PPAR gamma/*genetics
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Adrenergic, beta-2/*genetics
MH  - Receptors, Leptin/*genetics
MH  - Regression Analysis
MH  - Sex Characteristics
MH  - White People
EDAT- 2011/01/15 06:00
MHDA- 2011/09/14 06:00
CRDT- 2011/01/15 06:00
PHST- 2011/01/15 06:00 [entrez]
PHST- 2011/01/15 06:00 [pubmed]
PHST- 2011/09/14 06:00 [medline]
AID - oby2010325 [pii]
AID - 10.1038/oby.2010.325 [doi]
PST - ppublish
SO  - Obesity (Silver Spring). 2011 Jun;19(6):1244-51. doi: 10.1038/oby.2010.325. Epub 
      2011 Jan 13.