ABSTRACT Objective Monocyte chemoattractant protein 1 (MCP-1) has been suggested to be involved in the pathophysiology of insulin resistance (IR); therefore, variants in the MCP-1 gene may contribute to the development of this disease. The aim of this study was to analyze the relationship of the -2518 A>G MCP-1 (rs1024611) gene polymorphism with insulin resistance in Mexican children. Subjects and methods A cross-sectional study was performed in 174 children, including 117 children without insulin resistance and 57 children with IR, with an age range of 6-11 years. Levels for serum insulin and high-sensitivity C-reactive protein were determined. The -2518 A>G MCP-1 polymorphism was identified by the polymerase chain reaction-restriction fragment length polymorphism method. Insulin resistance was defined as a HOMA-IR in the upper 75th percentile, which was ≥ 2.4 for all children. Results Genotype frequencies of the rs1024611 polymorphism for the insulin-sensitive group were 17% AA, 48% AG and 35% GG, and the frequency of G allele was 59%, whereas frequencies for the insulin-resistant group were 12% AA, 37% AG and 51% GG, and the frequency of G allele was 69%. The genotype and allele frequencies between groups did not show significant differences. However, the GG genotype was the most frequent in children with IR. The GG genotype was associated with insulin resistance (OR = 2.2, P = 0.03) in a genetic model. Conclusion The -2518 A>G MCP-1 gene polymorphism may be related to the development of insulin resistance in Mexican children.

La presencia de la obesidad en la infancia predispone al desarrollo de enfermedades cardiovasculares y metabólicas, como la enfermedad arterial coronaria y la diabetes mellitus tipo 2 en la edad adulta. Algunos polimorfismos en el gen PAI-1 se han relacionado con la obesidad y el síndrome metabólico en varias poblaciones. El objetivo del estudio fue investigar la asociación de los polimorfismos -844 G/A (rs2227631), -675 4G/5G (rs1799889) y HindIII C/G (rs757716) en el gen PAI-1 con la obesidad y las dislipidemias en una muestra de niños mexicanos. Se realizó un estudio transversal en 222 niños con un rango de edad de 6-11 años, de los cuales 104 niños fueron clasificados con obesidad y 118 con peso normal. Los poli morfismos en el gen PAI-1 fueron analizados por PCR-RFLP. También se determinó el desequilibrio de ligamiento y el análisis de haplogenotipos de los tres polimorfismos. Los resultados mostraron la asociación significativa de la obesidad con el genotipo -844 G/A y el alelo A (OR= 2,75, p<0,001 y OR= 1,76, p=0,01, respectivamente). El polimorfismo -844 G/A se encontró en desequilibrio de ligamiento con el -675 4G/5G (D’= 0.77). También se encontró que el haplogenotipo G-4G-C/A-5G-G es un marcador de riesgo para la obesidad [OR=2,6; 95% intervalo de confianza (CI) 1,17-4,22; p= 0,01], además de que este haplogenotipo presentó una asociación marginal con la hipertrigliceridemia (OR= 2,6; 95% CI 1,04-6,35; p= 0,05). El haplogenotipo G-4G-C/A-5G-G en el gen PAI-1 puede ser un marcador genético de susceptibilidad para obesidad e hipertrigliceridemia en niños mexicanos.

The presence of childhood obesity predisposes to the development of cardio vascular and metabolic diseases, such as coronary artery disease and type 2 diabetes mellitus, in adulthood. The polymorphisms described in PAI-1 gene have been linked with obesity and metabolic syndrome in several populations. The aim of this study was to investigate the as sociation of the -844 G/A (rs2227631), -675 4G/5G (rs1799889) and HindIII C/G (rs757716) PAI-1 polymorphisms with obesity and dyslipidemia in a sample of Mexican children. A cross-sectional study was performed in 222 children with an age range between 6-11 years; 104 children were classified as obese and 118 children with normal-weight. The PAI-1 poly morphisms were analyzed by PCR-RFLP. Linkage disequilibrium (LD) and haplogenotype analysis among the three polymorphisms were determined. The results showed significant as sociations with obesity of the -844 G/A genotype and the A allele (OR= 2.75, p<0.001 and OR= 1.76, p=0.01, respectively). The -844 G/A polymorphism was found in LD with -675 4G/5G PAI-1 polymorphism (D’= 0.77). We found that G-4G-C/A-5G-G is a risk haplogeno type for obesity [OR=2.6; 95% confidence interval (CI) 1.17-4.22; p= 0.01] and with marginal association with hypertriglyceridemia(OR= 2.6; 95% CI 1.04-6.35; p= 0.05). The G-4G-C/A 5G-G PAI-1 haplogenotype may be a genetic marker of susceptibility for obesity and hypertri glyceridemia in Mexican children.

La obesidad se asocia con un estado de inflamación crónica de bajo grado. Generalmente, hay correlaciones significativas entre el índice de masa corporal y el incremento en los niveles de la proteína C reactiva (CRP). Se investigó la relación de los niveles de CRP de alta sensibilidad (hsCRP) con la distribución de la adiposidad corporal y la cuenta de las células sanguíneas en niños obesos. Se realizó un estudio transversal en 225 niños mexicanos. En el estudio se incluyeron 106 niños obesos y 119 con peso normal, edad de 6-13 años. La composición corporal fue evaluada por IMC, circunferencias corporales y grosor de pliegues cutáneos. Los niveles de la hsCRP de alta sensibilidad y los parámetros hematológicos fueron analizados en todos los niños. Los niveles de la hsCRP presentaron un incremento en los niños obesos con respecto al grupo control (1,5 y 0,41 mg/L respectivamente, P<0,001). Es interesante que los niveles de hsCRP>3 mg/L se asociaron con mayor circunferencia de cintura, cadera y brazo (ORs= 9,08, 6,78 y 8,73, respectivamente, P<0,001) y mayor grosor de los pliegues como tríceps, subescapular y suprailiaco (ORs= 4,73, 6,39 y 5,26, respectivamente, P=0,001), así como con el aumento en la cuenta de leucocitos y plaquetas. Los datos sugieren que los niveles de la hsCRP se asocian con el grosor de los pliegues cutáneos y las circunferencias corporales y fue encontrada una relación moderada con las cuentas de leucocitos y plaquetas en los niños estudiados.

Obesity is associated with a state of chronic low-grade inflammation. Generally, there are significant correlations between body mass index and increased C-reactive protein levels. We investigated the relationship of high sensitivity C-reactive protein (hsCRP) levels with body adiposity distribution and blood cell count in obese children. A cross-sectional study was performed in 225 Mexican children. In the study were included 106 obese and 119 normal-weight children, aged 6-13 years old. The body composition was evaluated by BMI, body circumferences and skinfold thickness. hsCRP levels and hematological parameters were analyzed in all children. The hsCRP levels were higher in obese children than in the control group (1.5 and 0.41 mg/L respectively, P<0.001). Interestingly, hsCRP levels >3 mg/L were associated with the increase of circumferences of the waist, hip and arms (ORs= 9.08, 6.78 and 8.73, respectively, P<0.001), and a higher thickness of triceps, subscapular and suprailiac skinfolds (ORs= 4.73, 6.39 and 5.26, respectively, P=0.001), as well as a higher leukocyte and platelet counts. The data suggest that hsCRP levels are associated with skinfold thickness and body circumferences, and a moderate relationship was found with leukocyte and platelet counts in the studied children.