PPARγ2 Pro12Ala Polymorphism is Associated in Children With Traits Related to Susceptibility to Type 2 Diabetes

被引:4
作者
Vales-Villamarin, Claudia [1 ]
de Dios, Olaya [1 ]
Perez-Nadador, Iris [1 ]
Gavela-Perez, Teresa [2 ]
Soriano-Guillen, Leandro [2 ]
Garces, Carmen [1 ]
机构
[1] IIS Fdn Jimenez Diaz UAM, Lipid Res Lab, Madrid, Spain
[2] IIS Fdn Jimenez Diaz UAM, Dept Pediat, Madrid, Spain
关键词
PPAR gamma 2 Pro12Ala polymorphism; insulin; HOMA; obesity; body mass index (BMI); children; PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA-2; BODY-MASS INDEX; PPAR-GAMMA; INSULIN-RESISTANCE; LIPID PROFILE; GENE POLYMORPHISMS; MISSENSE MUTATION; PEROXISOME; VARIANT; OBESITY;
D O I
10.3389/fphar.2021.763853
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated nuclear receptor that regulates glucose and lipid metabolism. Pharmacological activators of PPAR gamma are being used as a treatment of obesity related disorders such as dyslipidaemia and type 2 diabetes, but questions remain open regarding the effects of PPAR gamma on traits related to the development of type 2 diabetes. In our study, we have analyzed the relationship of the common variant Pro12Ala in the human PPAR gamma 2 gene with the presence of obesity and with insulin, HOMA and lipid profile in a representative sample of 6-to 8-year-old children free from the confounding factors associated with adults. We found that Ala12Ala genotype was significantly more frequent in females with obesity than in those without obesity, with Ala12Ala carriers having significantly higher weight and body mass index (BMI), however the association disappeared when adjusting by leptin concentrations. The Ala12Ala genotype was associated with significantly higher HDL-cholesterol and apoA-I levels in males but not in females, independently of BMI. In a recessive model, in females, leptin levels appeared higher in Ala12Ala carriers. Although no apparent differences were observed in any sex when analyzing insulin levels and HOMA among genotypes without adjusting, lower insulin levels and lower HOMA appeared associated with Ala12Ala carriers when adjusting for BMI and leptin levels. In summary, our data showed that leptin seems to be having an effect on the association between the PPAR gamma 2 Pro12Ala and BMI. Besides, after controlling for BMI and leptin, a protective effect of the Ala12Ala variant of the PPAR gamma 2 Pro12Ala polymorphism on insulin sensitivity is evident already in prepubertal children.
引用
收藏
页数:8
相关论文
共 55 条
[1]   The common PPARγ Pro12Ala polymorphism is associated with decreased risk of type 2 diabetes [J].
Altshuler, D ;
Hirschhorn, JN ;
Klannemark, M ;
Lindgren, CM ;
Vohl, MC ;
Nemesh, J ;
Lane, CR ;
Schaffner, SF ;
Bolk, S ;
Brewer, C ;
Tuomi, T ;
Gaudet, D ;
Hudson, TJ ;
Daly, M ;
Groop, L ;
Lander, ES .
NATURE GENETICS, 2000, 26 (01) :76-80
[2]   Association of the Pro12Ala variant in the peroxisome proliferator-activated receptor-γ2 gene with obesity in two Caucasian populations [J].
Beamer, BA ;
Yen, CJ ;
Andersen, BE ;
Muller, D ;
Elahi, D ;
Cheskin, LJ ;
Andres, R ;
Roth, J ;
Shuldiner, AR .
DIABETES, 1998, 47 (11) :1806-1808
[3]   EFFECT OF THE Pro12Ala POLYMORPHISM OF THE PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORγ2 GENE ON LIPID PROFILE AND ADIPOKINES LEVELS IN OBESE SUBJECTS [J].
Becer, E. ;
Cirakoglu, A. .
BALKAN JOURNAL OF MEDICAL GENETICS, 2017, 20 (01) :71-79
[4]   Obesity-Related Genetic Polymorphisms and Adiposity Indices in a Young Italian Population [J].
Bordoni, Laura ;
Marchegiani, Francesca ;
Piangerelli, Marco ;
Napolioni, Valerio ;
Gabbianelli, Rosita .
IUBMB LIFE, 2017, 69 (02) :98-105
[5]   PPAR-γ2 Pro12Ala variant is associated with greater insulin sensitivity in childhood obesity [J].
Buzzetti, R ;
Petrone, A ;
Caiazzo, AM ;
Alemanno, I ;
Zavarella, S ;
Capizzi, M ;
Mein, CA ;
Osborn, JA ;
Vania, A ;
Di Mario, U .
PEDIATRIC RESEARCH, 2005, 57 (01) :138-140
[6]   Leptin down-regulates peroxisome proliferator-activated receptor γ (PPARγ) mRNA levels in primary human monocyte-derived macrophages [J].
Cabrero, A ;
Cubero, M ;
Llaverías, G ;
Alegret, M ;
Sánchez, R ;
Laguna, JC ;
Vázquez-Carrera, M .
MOLECULAR AND CELLULAR BIOCHEMISTRY, 2005, 275 (1-2) :173-179
[7]   Thiazolidinediones and PPARγ agonists: time for a reassessment [J].
Cariou, Bertrand ;
Charbonnel, Bernard ;
Staels, Bart .
TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2012, 23 (05) :205-215
[8]   PPARγ and Diabetes: Beyond the Genome and Towards Personalized Medicine [J].
Cataldi, Simona ;
Costa, Valerio ;
Ciccodicola, Alfredo ;
Aprile, Marianna .
CURRENT DIABETES REPORTS, 2021, 21 (06)
[9]   The Pro12Ala and C-681G variants of the PPARG locus are associated with opposing growth phenotypes in young schoolchildren [J].
Cecil, JE ;
Fischer, B ;
Doney, ASF ;
Hetherington, M ;
Watt, P ;
Wrieden, W ;
Bolton-Smith, C ;
Palmer, CNA .
DIABETOLOGIA, 2005, 48 (08) :1496-1502
[10]   No clinical utility of common polymorphisms in IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 genes previously associated with insulin resistance in overweight children from Romania and Moldova [J].
Chirita-Emandi, Adela ;
Munteanu, Diana ;
Andreescu, Nicoleta ;
Tutac, Paul ;
Paul, Corina ;
Velea, Lulian Puiu ;
Pusztai, Agneta Maria ;
Hlistun, Victoria ;
Boiciuc, Chiril ;
Sacara, Victoria ;
Vudu, Lorina ;
Usurelu, Natalia ;
Puiu, Maria .
JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM, 2019, 32 (01) :33-39