Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children

de la Cruz-Mosso, Ulises; Muñoz-Valle, José Francisco; Salgado-Bernabé, Aralia Berenice; Castro-Alarcón, Natividad; Salgado-Goytia, Lorenzo; Sánchez-Corona, José; Flores-Martínez, Silvia Esperanza; Parra-Rojas, Isela

doi:10.1016/j.jpedp.2013.01.005

Informação do artigo

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Estatísticas

Abstract

Objective

To assess whether the -675 4G/5G polymorphism in the plasminogen activator inhibitor-1 gene is associated with obesity and insulin resistance in Mexican children.

Methods

A cross-sectional study was performed in 174 children, 89 with normal-weight and 85 with obesity, aged from 6 to 13 years. All children were from state of Guerrero, and recruited from three primary schools in the city of Chilpancingo, Mexico. Insulin levels were determined by immunoenzymatic assay. The homeostasis model assessment was used to determine insulin resistance. The -675 4G/5G polymorphism in PAI-1 gene was analyzed by polymerase chain reaction-restriction fragment length polymorphism.

Results

The prevalence of insulin resistance in the obese group was higher (49.41%) than in the normal-weight group (16.85%). The 4G/5G PAI-1 polymorphism was found in Hardy Weinberg equilibrium. The 4G/5G genotype contributed to a significant increase in waist-hip ratio (b = 0.02, p = 0.006), waist circumference (b = 4.42, p = 0.009), and subscapular skinfold thickness (b = 1.79, p = 0.04); however, it was not related with insulin resistance.

Conclusion

The -675 4G/5G genotype of PAI-1 gene was associated with increase of body adiposity in Mexican children.

Keywords:

PAI-1 gene

Polymorphisms

Body adiposity

Insulin resistance

Resumo

Objetivo

Elaboramos este estudo para avaliar se o polimorfismo -675 4G/5G no gene inibidor 1 do ativador do plasminogênio se associa à obesidade e à resistência insulínica em crianças mexicanas.

Métodos

Foi realizado um estudo transversal em 174 crianças, 89 delas com peso nor- mal e 85 obesas, variando sua idade de 6 a 13 anos. Todas as crianças eram do estado de Guerrero e foram recrutadas de três escolas primárias na cidade de Chilpancingo, México. Os níveis de insulina foram determinados por prova imunoenzimática. Foi usado o modelo de avaliação da homeostase para determinar resistência insulínica. O poli- morfismo -675 4G/5G no gene PAI-1 foi analisado pelo método reação de polimerase em cadeia-polimorfismo no comprimento dos fragmentos de restrição.

Resultados

A prevalência de resistência insulínica no grupo obeso foi mais alta (49,41%) do que no grupo com peso normal (16,85%). O polimorfismo 4G/5G do PAI-1 foi encon- trado em equilíbrio de Hardy Weinberg. O genótipo 4G/5G contribuiu para um aumento significativo da relação cintura-quadril (b = 0,02, p = 0,006), da circunferência da cintura (b = 4,42, p = 0,009) e da espessura da prega subescapular (b = 1,79, p = 0,04), mas não se relacionou com a resistência insulínica.

Conclusão

O genótipo -675 4G/5G do gene PAI-1 se associou a aumento da adiposidade corporal em crianças mexicanas.

Palavras-chave:

Gene PAI-1

Polimorfismos

Adiposidade corporal

Resistência insulínica

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References

[1]

D. Ozel Demiralp, H. Aktas, N. Akar.

The effect of plasminogen activator inhibitor-1-675 4G/5G polymorphism on PAI-1 gene expression and adipocyte differentiation.

Clin Appl Thromb Hemost., 14 (2008), pp. 438-446

http://dx.doi.org/10.1177/1076029607305081 | Medline

[2]

Y. Aso.

Plasminogen activator inhibitor (PAI)-1 in vascular inflammation and thrombosis.

Front Biosci., 12 (2007), pp. 2957-2966

Medline

[3]

B.R. Binder, G. Christ, F. Gruber, N. Grubic, P. Hufnagl, M. Krebs, et al.

Plasminogen activator inhibitor 1: physiological and pathophysiological roles.

News Physiol Sci., 17 (2002), pp. 56-61

Medline

[4]

H. Ha, E.Y. Oh, H.B. Lee.

The role of plasminogen activator inhibitor 1 in renal and cardiovascular diseases.

Nat Rev Nephrol., 5 (2009), pp. 203-211

http://dx.doi.org/10.1038/nrneph.2009.15 | Medline

[5]

Z. Ma, D. Paek, C.K. Oh.

Plasminogen activator inhibitor-1 and asthma: role in the pathogenesis and molecular regulation.

Clin Exp Allergy., 39 (2009), pp. 1136-1144

http://dx.doi.org/10.1111/j.1365-2222.2009.03272.x | Medline

[6]

C. Lopes, C. Dina, E. Durand, P. Froguel.

PAI-1 polymorphisms modulate phenotypes associated with the metabolic syndrome in obese and diabetic caucasian population.

Diabetologia., 46 (2003), pp. 1284-1290

http://dx.doi.org/10.1007/s00125-003-1170-0 | Medline

[7]

E.K. Kruithof.

Regulation of plasminogen activator inhibitor type 1 gene expression by inflammatory mediators and statins.

Thromb Haemost., 100 (2008), pp. 969-975

Medline

[8]

P.E. Morange, N. Saut, M.C. Alessi, J.S. Yudkin, M. Margaglione, G. Di Minno, et al.

Association of plasminogen activator inhibitor (PAI)-1 (SERPINE1) SNPs with myocardial infarction, plasma PAI- 1, and metabolic parameters: the HIFMECH study.

Arterioscler Thromb Vasc Biol., 27 (2007), pp. 2250-2257

http://dx.doi.org/10.1161/ATVBAHA.107.149468 | Medline

[9]

N.H. Naran, N. Chetty, N.J. Crowther.

The influence of metabolic syndrome components on plasma PAI-1 concentrations is modified by the PAI-1 4G/5G genotype and ethnicity.

Atherosclerosis., 196 (2008), pp. 155-163

http://dx.doi.org/10.1016/j.atherosclerosis.2007.03.024 | Medline

[10]

L. Bouchard, M.C. Vohl, S. Lebel, F.S. Hould, P. Marceau, J. Bergeron, et al.

Contribution of genetic and metabolic syndrome to omental adipose tissue PAI-1 gene mRNA and plasma levels in obesity.

Obes Surg., 20 (2010), pp. 492-499

http://dx.doi.org/10.1007/s11695-010-0079-1 | Medline

[11]

P. Eriksson, B. Kallin, F.M. van ‘t Hooft, P. Båvenholm, A. Hamsten.

Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction.

Proc Natl Acad Sci U S A., 92 (1995), pp. 1851-1855

Medline

[12]

L.J. McCormack, D.K. Nagi, M.H. Stickland, M.W. Mansfield, V. Mohamed-Ali, J.S. Yudkin, et al.

Promoter (4G/5G) plasminogen activator inhibitor-1 genotype in Pima Indians: relationship to plasminogen activator inhibitor-1 levels and features of the insulin resistance syndrome.

Diabetologia., 39 (1996), pp. 1512-1518

Medline

[13]

E.E. Kershaw, J.S. Flier.

Adipose tissue as an endocrine organ.

J Clin Endocrinol Metab., 89 (2004), pp. 2548-2556

http://dx.doi.org/10.1210/jc.2004-0395 | Medline

[14]

J. Hoffstedt, I.L. Andersson, L. Persson, B. Isaksson, P. Arner.

The common -675 4G/5G polymorphism in the plasminogen activator inhibitor -1 gene is strongly associated with obesity.

Diabetologia., 45 (2002), pp. 584-587

http://dx.doi.org/10.1007/s00125-001-0774-5 | Medline

[15]

I. Silva-Zolezzi, A. Hidalgo-Miranda, J. Estrada-Gil, J.C. Fernandez- Lopez, L. Uribe-Figueroa, A. Contreras, et al.

Analysis of genomic diversity in Mexican mestizo populations to develop genomic medicine in Mexico.

Proc Natl Acad Sci U S A., 106 (2009), pp. 8611-8616

http://dx.doi.org/10.1073/pnas.0903045106 | Medline

[16]

S. Ruiz-Quezada, M. Vázquez-Del Mercado, I. Parra-Rojas, H. Rangel- Villalobos, C. Best-Aguilera, L.V. Sánchez-Orozco, et al.

Genotype and allele frequency of PAI-1 promoter polymorphism in healthy subjects from the west of Mexico.

Association with biochemical and hematological parameters. Ann Genet., 47 (2004), pp. 155-162

[17]

I. Nuño-Arana, L.A. Páez-Riberos, L. Sando-val-Ramírez, J.M. Muñoz- Valle, D. Pinto-Escalante, J.M. Ceballos-Quintal, et al.

High prevalence of 5G allele in Amerindian tribes and mestizos from Mexico at 4G/5G PAI-I gene promoter polymorphism.

Thromb Haemost., 93 (2005), pp. 1005-1007

Medline

[18]

S.J. Dawson, B. Wiman, A. Hamsten, F. Green, S. Humphries, A.M. Henney.

The two allele sequences of a common polymorphism in the promoter of the plasminogen activator inhibitor-1 (PAI-1) gene respond differently to interleukin-1 in HepG2 cells.

J Biol Chem., 268 (1993), pp. 10739-10745

Medline

[19]

M. Henry, N. Chomiki, P.Y. Scarabin, M.C. Alessi, F. Peiretti, D. Arveiler, et al.

Five frequent polymorphisms of the PAI-1 gene: lack of association between genotypes PAI activity, and triglyceride levels in a healthy population.

Arterioscler Thromb Vasc Biol., 17 (1997), pp. 851-858

Medline

[20]

K. Yamamoto, H. Saito.

A pathological role of increased expression of plasminogen activator inhibitor-1 in human or animal disorders.

Int J Hematol., 68 (1998), pp. 371-385

Medline

[21]

I. Juhan-Vague, M.C. Alessi, P.E. Morange.

Hypofibrinolysis and increased PAI-1 are linked to atherothrombosis via insulin resistance and obesity.

Ann Med., 32 (2000), pp. 78-84

Medline

[22]

J.P. Bastard, L. Piéroni, B. Hainque.

Relationship between plasma plasminogen activator inhibitor 1 and insulin resistance.

Diabetes Metab Res Rev., 16 (2000), pp. 192-201

Medline

[23]

P.E. Morange, H.R. Lijnen, M.C. Alessi, F. Kopp, D. Collen, I. Juhan-Vague.

Influence of PAI-1 on adipose tissue growth and metabolic parameters in a murine model of diet-induced obesity.

Arterioscler Thromb Vasc Biol., 20 (2000), pp. 1150-1154

Medline

[24]

K. Schäfer, K. Fujisawa, S. Konstantinides, D.J. Loskutoff.

Disruption of the plasminogen activator inhibitor 1 gene reduces the adiposity and improves the metabolic profile of genetically obese and diabetic ob/ob mice.

FASEB J., 15 (2001), pp. 1840-1842

Medline

☆

Como citar este artigo: de la Cruz-Mosso U, Muñoz-Valle JF, Salgado-Bernabé AB, Castro-Alarcón N, Salgado-Goytia L, Sánchez-Corona J, et al. Body adiposity but not insulin resistance is associated with -675 4G/5G polymorphism in the PAI-1 gene in a sample of Mexican children. J Pediatr (Rio J). 2013;89:492-8.

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