Effects of Foods of Mesoamerican Origin in Adipose Tissue and Liver-Related Metabolism.

Adipose tissue and liver metabolism play a key role in maintaining body homeostasis; therefore, their impairment conduces a pathological state. Nowadays, occidental lifestyle is a common etiological issue among a variety of chronic diseases, while diet is a unique strategy to prevent obesity and liver metabolism impairment and is a powerful player in the treatment of metabolic-related diseases. Mesoamerican foods are rich in bioactive molecules that enhance and improve adipose tissue and liver performance and represent a prophylactic and therapeutic alternative for disorders related to the loss of homeostasis in the metabolism of these two important tissues.

Firmicutes, Bacteroidetes and Actinobacteria in Human Milk and Maternal Adiposity.

The main objective was to explore the relationship between the microbiota of human milk and adiposity in Mexican mothers during the first lactation stage. METHODS: Seventy lactating women were included. Adiposity by anthropometric measurements and by bioelectric impedance was obtained. The donation of human milk was requested, from which bacterial DNA was extracted and qPCR of the 16S region was performed. The Mann-Whitney U test, Spearman and Pearson correlations, and multiple linear regressions models were also calculated. RESULTS: The median percentage of Bacteroidetes had a direct and significant correlation with normal adiposity, current BMI, waist circumference, and body fat percentage. The correlation with current BMI became significantly inverse in women with BMI ≥ 25. In women with normal BMI, the percentage of Actinobacteria showed a direct and significant correlation with current BMI, waist circumference, and percentage of body fat. Multiple linear regressions showed that pre-pregnancy BMI was the variable with the highest predictive value with the Bacteroidetes phyla in normal BMI and in BMI ≥ 25. CONCLUSIONS: the adiposity of the woman before pregnancy and during lactation would have an important effect on the abundance of Bacteroidetes and Actinobacteria in human milk.

Ageing influences the relationship of circulating miR-33a and miR- 33b levels with insulin resistance and adiposity.

OBJECTIVE: The identification of circulating microRNAs related to abnormal metabolic function may be useful in the context of ageing, adiposity and insulin resistance. The miR-33 a/b has been shown to control the expression of genes involved in fatty acid biosynthesis, impaired metabolism and insulin resistance. In this study, we aimed to identify differences in circulating miR-33 a/b levels according to age-related metabolic impairment and increased adiposity. METHODS: This study included 80 individuals (30.2% with obesity, 70% females) classified according to insulin resistance (Stern's criteria) and age [young (20-39 years) and senior (40-59 years)]. Body fat was evaluated using bioelectrical impedance, biochemical markers by colorimetric, enzymatic and immuno-turbidimetry methods. TaqMan measures of circulating miR-33 a and miR-33 b with quantitative reverse transcription polymerase chain reaction in serum were assessed in association with clinical outputs. RESULTS: Circulating miR-33 a and miR-33 b levels showed significant association with fatness, the lipid profile and biomarkers of impaired glucose metabolism. Both miR-33 a and miR-33 b were associated with visceral adiposity index in non-insulin resistance and insulin resistance individuals. More important, for miR-33 a circulating levels in senior group, receiver operating characteristic curve analyses showed area under the curve 0.804 ( p = 0.010; 95% confidence interval = 0.655-0.952). CONCLUSION: Ageing influenced the relationship of circulating miR-33 a and miR-33 b with insulin resistance and increased adiposity.

F8 inversions of introns 22 and 1 confer a moderate risk of inhibitors in Mexican patients with severe hemophilia A. Concordance analysis and literature review.

Intron-22 (Inv22) and intron-1 (Inv1) inversions account for approximately one half of all severe cases of hemophilia A (SHA) worldwide. Inhibitor development against exogenous factor VIII (FVIII) represents a major complication in HA. The causative F8 mutation is considered the most decisive factor conditioning inhibitor development. We aimed to investigate prevalence of Inv22 and Inv1 mutations, and its association as risk factors for developing inhibitors to FVIII. We investigated Inv22 and Inv1 in 255 SHA Mexican patients from 193 unrelated families using the inverse shifting-polymerase chain reaction (IS-PCR). We analyzed the association between inversions and inhibitor development via logistic regression introducing as covariates the populations, the inversions, F8-haplotypes and the age of patients at enrollment. Inv22 was found in 91/193 (47.2%: 38.9% exhibited Inv22-1 and 8.3% Inv22-2), and Inv1 in 2/193 (1.0%) independent families. Absolute inhibitor prevalence (IP) for Inv22 in unrelated patients was 15% (10-19). The cohorts and age of patients were independent predictors of inhibitor risk, but not inversions or haplotypes. Inversions presence in our population was associated to a moderate risk of developing inhibitors. Inv1 was found for the first time in two Mexican families. A relevant genetic component was observed by the strong concordance among brother-pairs.

Low CD36 and LOX-1 Levels and CD36 Gene Subexpression Are Associated with Metabolic Dysregulation in Older Individuals with Abdominal Obesity.

Background. Obesity study in the context of scavenger receptors has been linked to atherosclerosis. CD36 and LOX-1 are important, since they have been associated with atherogenic and metabolic disease but not fat redistribution. The aim of our study was to determinate the association between CD36 and LOX-1 in presence of age and abdominal obesity. Methods. This is a cross-sectional study that included 151 healthy individuals, clinically and anthropometrically classified into two groups by age (<30 and ≥30 years old) and abdominal obesity (according to World Health Organization guidelines). We excluded individuals with any chronic and metabolic illness, use of medication, or smoking. Fasting blood samples were taken to perform determination of CD36 mRNA expression by real-time PCR, lipid profile and metabolic and low grade inflammation markers by routine methods, and soluble scavenger receptors (CD36 and LOX-1) by ELISA. Results. Individuals ≥30 years old with abdominal obesity presented high atherogenic index, lower soluble scavenger receptor levels, and subexpression of CD36 mRNA (54% less). On the other hand, individuals <30 years old with abdominal adiposity presented higher levels in the same parameters, except LOX-1 soluble levels. Conclusion. In this study, individuals over 30 years of age presented low soluble scavenger receptors levels pattern and CD36 gene subexpression, which suggest the chronic metabolic dysregulation in abdominal obesity.

Inverse Relationship of the CMKLR1 Relative Expression and Chemerin Serum Levels in Obesity with Dysmetabolic Phenotype and Insulin Resistance.

BACKGROUND: In obesity there is a subclinical chronic low-grade inflammatory response where insulin resistance (IR) may develop. Chemerin is secreted in white adipose tissue and promotes low-grade inflammatory process, where it expressed CMKLR1 receptor. The role of chemerin and CMKLR1 in inflammatory process secondary to obesity is not defined yet. METHODS: Cross-sectional study with 134 individuals classified as with and without obesity by body mass index (BMI) and IR. Body fat storage measurements and metabolic and inflammatory markers were measured by routine methods. Soluble chemerin and basal levels of insulin by ELISA and relative expression of CMKLR1 were evaluated with qPCR and 2(-ΔΔCT) method. RESULTS: Differences (P < 0.05) were observed between obesity and lean individuals in body fat storage measurements and metabolic-inflammatory markers. Both CMKLR1 expression and chemerin levels were increased in obesity without IR. Soluble chemerin levels correlate with adiposity and metabolic markers (r = 8.8% to 38.5%), P < 0.05. CONCLUSION: The increment of CMKLR1 expression was associated with insulin production. Increased serum levels of chemerin in obesity were observed, favoring a dysmetabolic response. The results observed in this study suggest that both chemerin and CMKLR1 have opposite expression in the context of low-grade inflammatory response manifested in the development of IR.

CCL2 Serum Levels and Adiposity Are Associated with the Polymorphic Phenotypes -2518A on CCL2 and 64ILE on CCR2 in a Mexican Population with Insulin Resistance.

Genetic susceptibility has been described in insulin resistance (IR). Chemokine (C-C motif) ligand-2 (CCL2) is overexpressed in white adipose tissue and is the ligand of C-C motif receptor-2 (CCR2). The CCL2 G-2518A polymorphism is known to regulate gene expression, whereas the physiological effects of the CCR2Val64Ile polymorphism are unknown. The aim of the study is to investigate the relationship between these polymorphisms with soluble CCL2 levels (sCCL2), metabolic markers, and adiposity. In a cross-sectional study we included 380 Mexican-Mestizo individuals, classified with IR according to Stern criteria. Polymorphism was identified using PCR-RFLP/sequence-specific primers. Anthropometrics and metabolic markers were measured by routine methods and adipokines and sCCL2 by ELISA. The CCL2 polymorphism was associated with IR (polymorphic A+ phenotype frequencies were 70.9%, 82.6%, in individuals with and without IR, resp.). Phenotype carriers CCL2 (A+) displayed lower body mass and fat indexes, insulin and HOMA-IR, and higher adiponectin levels. Individuals with IR presented higher sCCL2 compared to individuals without IR and was associated with CCR2 (Ile+) phenotype. The double-polymorphic phenotype carriers (A+/Ile+) exhibited higher sCCL2 than double-wild-type phenotype carriers (A-/Ile-). The present findings suggest that sCCL2 production possibly will be associated with the adiposity and polymorphic phenotypes of CCL2 and CCR2, in Mexican-Mestizos with IR.

The 482Ser of PPARGC1A and 12Pro of PPARG2 Alleles Are Associated with Reduction of Metabolic Risk Factors Even Obesity in a Mexican-Mestizo Population.

The aim of this study was to investigate the relationship between functional polymorphisms Gly482Ser in PPARGC1A and Pro12Ala in PPARG2 with the presence of obesity and metabolic risk factors. We included 375 individuals characterized as Mexican-Mestizos and classified by the body mass index (BMI). Body dimensions and distribution of body fat were measured. The HOMA-IR and adiposity indexes were calculated. Adipokines and metabolic profile quantification were performed by ELISA and routine methods. Genetic polymorphisms were determined by polymerase chain reaction restriction fragment length polymorphism analysis. A difference between obese and nonobese subjects in polymorphism PPARGC1A distribution was observed. Among obese individuals, carriers of genotype 482Gly/Gly were observed to have decreased body fat, BMI, and body fat ratio versus 482Ser/Ser carriers and increased resistin and leptin levels in carriers Gly+ phenotype versus Gly- phenotype. Subjects with PPARG2 Ala- phenotype (genotype 12Pro/Pro) showed a decreased HOMA-IR index versus individuals with Ala+ phenotype (genotypes 12Pro/Ala plus 12Ala/Ala). We propose that, in obese Mexican-Mestizos, the combination of alleles 482Ser in PPARGC1A and 12Pro in PPARG2 represents a reduced metabolic risk profile, even when the adiposity indexes are increased.

The Impact of LEP G-2548A and LEPR Gln223Arg Polymorphisms on Adiposity, Leptin, and Leptin-Receptor Serum Levels in a Mexican Mestizo Population.

The polymorphisms in leptin (LEP G-2548A) and leptin-receptor (LEPR Gln223Arg) seem to influence obesity and lipid metabolism among others. The aim of this study was to investigate the effect of these polymorphisms on adiposity, leptin (sLeptin), and leptin-receptor (sLeptin-receptor) serum concentrations as well as inflammation markers. We included 382 adults originally from Western Mexico. They were genotyped by PCR-RFLP. Obese individuals showed higher sLeptin (58.2 ± 31.35 ng/mL) but lower sLeptin-receptor (12.6 ± 3.74 ng/mL) levels than normal weight ones (17.6 ± 14.62 ng/mL, 17.4 ± 4.62 ng/mL, resp.), P < 0.001. Obese subjects carriers of Arg/Arg genotype had more (P = 0.016) sLeptin-receptor (14.7 ± 4.96 ng/mL) and less (P = 0.004) sLeptin (44.0 ± 28.12 ng/mL) levels than Gln/Gln genotype (11.0 ± 2.92 ng/mL, 80.3 ± 33.24 ng/mL, resp.). Body fat mass was lower (P from 0.003 to 0.045) for A/A (36.5% ± 6.80) or Arg/Arg (36.8% ± 6.82) genotypes with respect to G/G (41.3% ± 5.52) and G/A (41.6% ± 5.61) or Gln/Gln (43.7% ± 4.74) and Gln/Arg (41.0% ± 5.52) genotypes carriers. Our results suggest that LEP -2548A and LEPR 223Arg could be genetic markers of less body fat mass accumulation in obese subjects from Western Mexico.

Asociación del polimorfismo 3’UTR+62G>A en resistina con resistencia a la insulina, adiposidad y el índice adiponectina-resistina en población mexicana / Association of resistin gene 3’utr +62g>a polymorphism with insulin resistance, adiposity and the adiponectin-resistin index in Mexican population

Introduction: Insulin resistance (IR) is a disease with genetic susceptibility characterized by the increase in storage and irregular body fat distribution, and impaired production of adipokines. Objective: The objective was to investigate the relationship between 3'UTR+62G>A RETN gene polymorphism, with adiponectin-resistin index (ARindex), adiposity, and inmuno-metabolic markers. Methods: In this cross-sectional study, 260 individuals characterized as Mexican-Mestizo and classified in lean and overweight, and IR and without-IR, were included. Anthropometrics, body composition, body fat distribution and inflammation and metabolic markers were measured by routine methods, RETN 3'UTR+62G>A alleles were identified by PCR-RFLP and soluble insulin, total adiponectin and resistin were measured by ELISA methods. Results: The +62G allele frequencies for lean and overweight individuals were different P=0.0343 (95.4% and 98.4%, respectively). The lean GA genotype carriers showed significant low measures of ARindex, adiposity, and inmuno-metabolic markers, than the GG genotype carriers. We found differences between individuals with IR and without-IR: in ARindex (P=0.002), adiponectin (P=0.002) and resistin levels (P=0.033): 1.102 ± 0.03, 5.167 ± 0.36ug/mL and 8.827 ± 0.42ng/mL versus 1.336 ± 0.07, 3.577 ± 0.34ug/mL and 10.480 ± 0.65ng/mL. Showed correlations with inflammation markers, distribution and body fat storage (r=0.262 to 0.414), PA polymorphism is associated with overweight. The presence of the +62A allele was associated with increase of total adiponectin, ARindex, resistin levels, metabolic markers and body fat storage. ARindex can be an early indicator of insulin resistance (AU)

Introducción: La resistencia a la insulina (RI) se caracteriza por susceptibilidad genética, incremento en la adiposidad y distribución irregular de grasa corporal, con alteración en la producción de adipocinas. Objetivo: Investigar la asociación del polimorfismo 3’UTR+62G>A en resistina con RI, índice adiponectina-resistina (ARindex), adiposidad y marcadores inmuno-metabólicos. Métodos: En un estudio transversal a 260 mestizos-mexicanos, clasificados con peso normal, exceso de peso, sin y con RI, se les evaluó: composición corporal, distribución de masa grasa y marcadores inmuno-metabólicos. Los alelos del polimorfismo 3’UTR+62G>A en resistina se identificaron por PCR-RFLP. La concentración sérica de insulina, adiponectina total y resistina se midieron por la técnica de ELISA. Resultados: Las frecuencias del alelo +62G para los individuos con peso normal y exceso de peso, fueron (95.4% y 98.4%, respectivamente) P=0.0343. Los portadores del genotipo GA con peso normal mostraron valores menores del ARindex, adiposidad y marcadores inmuno-metabólicos comparados con los portadores del genotipo GG. Se observó diferencia entre los individuos sin y con RI en el ARindex (P=0.002), concentración sérica de adiponectina (P=0.002) y resistina (P=0.033): 1.102±0.03, 5.167±0.36ug/mL y 8.827±0.42ng/mL versus 1.336±0.07, 3.577±0.34ug/mL y 10.480±0.65ng/mL, respectivamente. Los marcadores inmuno-metabólicos, reserva y distribución de grasa corporal correlacionan con ARindex (r=0.262 a 0.414), PA en los individuos mestizos-mexicanos con exceso de peso. El alelo +62A se asoció con incremento de adiponectina total, valores menores del ARindex, concentración de resistina, marcadores metabólicos y reserva de grasa corporal. El ARindex puede ser un indicador temprano de RI (AU)

Porcentaje de adiposidad y su relación con el índice de inmunorreactividad de los receptores hormonales en mujeres mexicanas con cáncer de mama / Adiposity percentage relationship with hormone receptors immunoreactive score in breast cancer Mexican women

INTRODUCTION: Adipose tissue is an important estrogen resource and they are involved in breast cancer development. OBJECTIVE: To establish the relationship between adiposity percentage and the estrogen and progesterone receptors immunoreactive score in Mexican women with breast cancer. METHODS: This is a transversal and analytical study. We identified breast cancer women with cancer histologic diagnosis. We calculated: adiposity percentage and immunoreactive score. We performed correlation analysis between adiposity percentage, body mass index, diabetes mellitus and arterial hypertension, with estrogen and progesterone receptors in breast cancer samples. We perform logistic regression and Odds Ratio estimations. RESULTS: We studied 43 patients with breast cancer and we observed association between adiposity percentage and estrogen and progesterone immnunoreactive score (rP 0.470; p 0.003 and rP 0.328; p 0.042, respectively). The most important risk factor in breast cancer positive to estrogen receptors was obesity (OR 19.1, IC95% 2.1 a 169.1, p 0.008), and previous obesity in breast cancer positive to progesterone receptors (OR 20.7, IC95% 2.3 a 185.9, p 0.007). DISCUSSION: Adiposity percentage is an important risk factor to develop breast cancer positive to hormone receptors related with the risk of breast cancer positive to hormonal receptors (AU)

Introducción: El tejido adiposo es una importante fuente de estrógenos, los cuales se encuentran implicados en el desarrollo de cáncer de mama. Objetivo: Establecer la relación entre el porcentaje de adiposidad y el índice de inmunorreactividad de los receptores a estrógenos y a progesterona en mujeres mexicanas con cáncer de mama. Métodos: Estudio transversal analítico en pacientes con cáncer de mama confirmado con estudio histopatológico. Se estimó el % de adiposidad, y el índice de inmunorreactividad. Se realizó el análisis de correlación entre el porcentaje de adiposidad, el IMC, la presencia de DM2 e hipertensión arterial con la expresión de receptores a estrógeno y progesterona y regresión logística con cálculo de Odds Ratio. Resultados: Se estudiaron 43 pacientes con cáncer de mama y se observó asociación entre el porcentaje de adiposidad y el índice de inmunoreactividad para los RE y RP (rP 0,470; p 0,003 y rP 0,328; p 0,042 respectivamente). El factor de riesgo más importante en cáncer positivo a receptores estrogénicos fue la obesidad (OR 19,1, IC 95% 2,1 a 169,1, p 0,008) y obesidad previa en cáncer positivo a receptores a progesterona (OR 20,7, IC 95% 2,3 a 185,9, p 0,007). Conclusión: El porcentaje de adiposidad es un factor de riesgo importante para desarrollar cáncer de mama positivo a receptores hormonales (AU)

[Adiposity percentage relationship with hormone receptors immunoreactive score in breast cancer mexican women]. / Porcentaje de adiposidad y su relación con el índice de inmunorreactividad de los receptores hormonales en mujeres mexicanas con cáncer de mama.

INTRODUCTION: Adipose tissue is an important estrogen resource and they are involved in breast cancer development. OBJECTIVE: To establish the relationship between adiposity percentage and the estrogen and progesterone receptors immunoreactive score in Mexican women with breast cancer. METHODS: This is a transversal and analytical study. We identified breast cancer women with cancer histologic diagnosis. We calculated: adiposity percentage and immunoreactive score. We performed correlation analysis between adiposity percentage, body mass index, diabetes mellitus and arterial hypertension, with estrogen and progesterone receptors in breast cancer samples. We perform logistic regression and Odds Ratio estimations. RESULTS: We studied 43 patients with breast cancer and we observed association between adiposity percentage and estrogen and progesterone immnunoreactive score (rP 0.470; p 0.003 and rP 0.328; p 0.042, respectively). The most important risk factor in breast cancer positive to estrogen receptors was obesity (OR 19.1, IC95% 2.1 a 169.1, p 0.008), and previous obesity in breast cancer positive to progesterone receptors (OR 20.7, IC95% 2.3 a 185.9, p 0.007). DISCUSSION: Adiposity percentage is an important risk factor to develop breast cancer positive to hormone receptors related with the risk of breast cancer positive to hormonal receptors.

Introducción: El tejido adiposo es una importante fuente de estrógenos, los cuales se encuentran implicados en el desarrollo de cáncer de mama. Objetivo: Establecer la relación entre el porcentaje de adiposidad y el índice de inmunorreactividad de los receptores a estrógenos y a progesterona en mujeres mexicanas con cáncer de mama. Métodos: Estudio transversal analítico en pacientes con cáncer de mama confirmado con estudio histopatológico. Se estimó el % de adiposidad, y el índice de inmunorreactividad. Se realizó el análisis de correlación entre el porcentaje de adiposidad, el IMC, la presencia de DM2 e hipertensión arterial con la expresión de receptores a estrógeno y progesterona y regresión logística con cálculo de Odds Ratio. Resultados: Se estudiaron 43 pacientes con cáncer de mama y se observó asociación entre el porcentaje de adiposidad y el índice de inmunoreactividad para los RE y RP (rP 0,470; p 0,003 y rP 0,328; p 0,042 respectivamente). El factor de riesgo más importante en cáncer positivo a receptores estrogénicos fue la obesidad (OR 19,1, IC 95% 2,1 a 169,1, p 0,008) y obesidad previa en cáncer positivo a receptores a progesterona (OR 20,7, IC 95% 2,3 a 185,9, p 0,007). Conclusión: El porcentaje de adiposidad es un factor de riesgo importante para desarrollar cáncer de mama positivo a receptores hormonales.

[Association of resistin gene 3'UTR+62G>A polymorphism with insulin resistance, adiposity and the adiponectin-resistin index in Mexican population]. / Asociación del polimorfismo 3'UTR+62G>A en resistina con resistencia a la insulina, adiposidad y el índice adiponectina-resistina en población mexicana.

INTRODUCTION: Insulin resistance (IR) is a disease with genetic susceptibility characterized by the increase in storage and irregular body fat distribution, and impaired production of adipokines. OBJECTIVE: The objective was to investigate the relationship between 3'UTR+62G>A RETN gene polymorphism, with adiponectin-resistin index (ARindex), adiposity, and inmuno-metabolic markers. METHODS: In this cross-sectional study, 260 individuals characterized as Mexican-Mestizo and classified in lean and overweight, and IR and without-IR, were included. Anthropometrics, body composition, body fat distribution and inflammation and metabolic markers were measured by routine methods, RETN 3'UTR+62G>A alleles were identified by PCR-RFLP and soluble insulin, total adiponectin and resistin were measured by ELISA methods. RESULTS: The +62G allele frequencies for lean and overweight individuals were different P=0.0343 (95.4% and 98.4%, respectively). The lean GA genotype carriers showed significant low measures of ARindex, adiposity, and inmuno-metabolic markers, than the GG genotype carriers. We found differences between individuals with IR and without-IR: in ARindex (P=0.002), adiponectin (P=0.002) and resistin levels (P=0.033): 1.102 ± 0.03, 5.167 ± 0.36 ug/mL and 8.827 ± 0.42 ng/mL versus 1.336 ± 0.07, 3.577 ± 0.34 ug/mL and 10.480 ± 0.65 ng/mL. Showed correlations with inflammation markers, distribution and body fat storage (r=0.262 to 0.414), P< 0.05. CONCLUSIONS: The present data suggest that in a Mexican-mestizo population the RETN +62G>A polymorphism is associated with overweight. The presence of the +62A allele was associated with increase of total adiponectin, ARindex, resistin levels, metabolic markers and body fat storage. ARindex can be an early indicator of insulin resistance.

Introducción: La resistencia a la insulina (RI) se caracteriza por susceptibilidad genética, incremento en la adiposidad y distribución irregular de grasa corporal, con alteración en la producción de adipocinas. Objetivo: Investigar la asociación del polimorfismo 3'UTR+62G>A en resistina con RI, índice adiponectina-resistina (ARindex), adiposidad y marcadores inmuno-metabólicos. Métodos: En un estudio transversal a 260 mestizos-mexicanos, clasificados con peso normal, exceso de peso, sin y con RI, se les evaluó: composición corporal, distribución de masa grasa y marcadores inmuno-metabólicos. Los alelos del polimorfismo 3'UTR+62G>A en resistina se identificaron por PCR-RFLP. La concentración sérica de insulina, adiponectina total y resistina se midieron por la técnica de ELISA. Resultados: Las frecuencias del alelo +62G para los individuos con peso normal y exceso de peso, fueron (95.4% y 98.4%, respectivamente) P=0.0343. Los portadores del genotipo GA con peso normal mostraron valores menores del ARindex, adiposidad y marcadores inmuno-metabólicos comparados con los portadores del genotipo GG. Se observó diferencia entre los individuos sin y con RI en el ARindex (P=0.002), concentración sérica de adiponectina (P=0.002) y resistina (P=0.033): 1.102±0.03, 5.167±0.36ug/mL y 8.827±0.42ng/mL versus 1.336±0.07, 3.577±0.34ug/mL y 10.480±0.65ng/mL, respectivamente. Los marcadores inmuno-metabólicos, reserva y distribución de grasa corporal correlacionan con ARindex (r=0.262 a 0.414), PA en los individuos mestizos-mexicanos con exceso de peso. El alelo +62A se asoció con incremento de adiponectina total, valores menores del ARindex, concentración de resistina, marcadores metabólicos y reserva de grasa corporal. El ARindex puede ser un indicador temprano de RI.

PAI-1 mRNA expression and plasma level in rheumatoid arthritis: relationship with 4G/5G PAI-1 polymorphism.

Rheumatoid arthritis (RA) is a chronic inflammatory disease affecting the synovial membrane, cartilage and bone. PAI-1 is a key regulator of the fibrinolytic system through which plasminogen is converted to plasmin. The plasmin activates the matrix metalloproteinase system, which is closely related with the joint damage and bone destruction in RA. The aim of this study was to investigate the relationship between 4G/5G PAI-1 polymorphism with mRNA expression and PAI-1 plasma protein levels in RA patients. 113 RA patients and 123 healthy subjects (HS) were included in the study. The 4G/5G PAI-1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism method; the PAI-1 mRNA expression was determined by real-time PCR; and the soluble PAI-1 (sPAI-1) levels were quantified using an ELISA kit. No significant differences in the genotype and allele frequencies of 4G/5G PAI-1 polymorphism were found between RA patients and HS. However, the 5G/5G genotype was the most frequent in both studied groups: RA (42%) and HS (44%). PAI-1 mRNA expression was slightly increased (0.67 fold) in RA patients with respect to HS (P = 0.0001). In addition, in RA patients, the 4G/4G genotype carriers showed increased PAI-1 mRNA expression (3.82 fold) versus 4G/5G and 5G/5G genotypes (P = 0.0001), whereas the sPAI-1 plasma levels did not show significant differences. Our results indicate that the 4G/5G PAI-1 polymorphism is not a marker of susceptibility in the Western Mexico. However, the 4G/4G genotype is associated with high PAI-1 mRNA expression but not with the sPAI-1 levels in RA patients.

The functional class evaluated in rheumatoid arthritis is associated with soluble TGF-ß1 serum levels but not with G915C (Arg25Pro) TGF-ß1 polymorphism.

The influence of genetic factors in rheumatoid arthritis (RA) has been described, including several cytokine genes such as transforming growth factor ß (TGF-ß) with regulatory effects on lymphocytes, dendritic cells, macrophages, chondrocytes, and osteoblasts, which are important in the RA pathogenesis. The G915C TGF-ß1 polymorphism has been associated with soluble TGF-ß1 (sTGF-ß) serum levels. Thus, we studied the association of G915C (Arg25Pro) TGF-ß1 polymorphism with sTGF-ß1 serum levels in RA. We enrolled 120 RA patients and 120 control subjects (CS). The G915C TGF-ß1 polymorphism was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method, and sTGF-ß1 serum levels were quantified using an ELISA kit. The genotype frequency of G915C TGF-ß1 polymorphism in RA and CS was G/G (91.7%), G/C (8.3%), C/C (0%) and G/G (85.8%), G/C (14.2%), C/C (0%), respectively, without significant differences. Moreover, the G/G TGF-ß1 genotype carriers presented the highest disability index evaluated for the Spanish HAQ-DI score (P < 0.001). In addition, the sTGF-ß1 serum levels were higher in RA (182.2 ng/mL) than CS (160.2 ng/mL), there was not significant difference. However, we found a positive correlation between the sTGF-ß1 serum levels and the functional class (r = 0.472, P = 0.023). In conclusion, the G915C (Arg25Pro) TGF-ß1 polymorphism is not associated with RA, but the sTGF-ß1 serum levels are related with the functional class in RA.

Tumor necrosis factor alpha-308 and -238 polymorphisms in rheumatoid arthritis. Association with messenger RNA expression and sTNF-alpha.

BACKGROUND: Rheumatoid arthritis (RA) is characterized by a progressive joint damage mediated mainly by tumor necrosis factor alpha (TNFalpha). We investigated the relationship of TNFalpha-308 and -238 polymorphisms with messenger RNA (mRNA) expression and soluble TNFalpha (sTNFalpha) in 50 RA and 100 healthy subjects (HS). METHODS: Clinical and laboratory assessments were performed. Spanish Health Assessment Questionnaire Disability Index, Spanish version of Arthritis Impact Measurement Scales and Disease Activity Score using 28 joint count indices were applied to RA patients. The TNFalpha-308 and -238 polymorphisms were performed by polymerase chain reaction and restriction fragment length polymorphism techniques. The mRNA expression of TNFalpha was quantified by real-time polymerase chain reaction. The sTNFalpha levels were measured by enzyme-linked immunosorbent assay. RESULTS: The TNFalpha-308 polymorphism showed an increased frequency of guanine (G)/adenine (A) genotype in RA versus HS (P = 0.03; 95% confidence interval, 1.05-8.08; odds ratio, 2.9) and also the A allele was more frequent in RA patients versus HS (P = 0.04; 95% confidence interval, 1.01-7.29; odds ratio, 2.7). The G/G genotype and also the G allele were more frequent in HS. No significant difference was observed in TNFalpha-238 polymorphism. Rheumatoid arthritis patients showed high TNFalpha mRNA expression (1.33-fold). The G/G genotype was associated with high mRNA and sTNFalpha levels in both TNFalpha polymorphisms. The correlation of sTNFalpha levels with C-reactive protein, erythrocyte sedimentation rate, rheumatoid factor, Spanish Health Assessment Questionnaire Disability Index, and Spanish version of Arthritis Impact Measurement Scales, was observed. CONCLUSION: The TNFalpha-308 polymorphism is a susceptibility marker to RA. The G/G genotype is associated with a high mRNA and soluble TNFalpha expression.

sE-Selectin expression and A561C polymorphism in relation to rheumatoid arthritis clinical activity.

OBJECTIVE: To investigate the relationship of A561C polymorphism and sE-selectin levels with rheumatoid arthritis (RA) clinical activity. METHODS: In a case-control study, we compared 60 patients with RA and 60 healthy subjects. Patients fulfilled the 1987 American College of Rheumatology criteria. Soluble E-selectin levels were measured from serum samples using the ELISA kit. We investigated E-selectin A561C polymorphism by the restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. The disease activity was recorded with Spanish Health Assessment Questionnaire Disability Index (HAQ-DI), Spanish Arthritis Impact Measurement Scales (AIMS), and Disease Activity Score (DAS28) scores. A p value < 0.05 was considered significant. RESULTS: Patients with RA showed higher sE-selectin levels than controls (mean 91.7 vs 39 ng/ml; p = 0.002). A positive correlation between sE-selectin and rheumatoid factor (RF), erythrocyte sedimentation rate (ESR), Spanish HAQ-DI, and DAS28 scores was found. The E-selectin polymorphism analysis showed diminished frequency in RA of heterozygous A/C genotype and increased frequency of homozygous wild-type A/A genotype (p = 0.043, OR 1.45; 95% CI 1.125-16.167) versus A/C and A/A genotype in healthy subjects. No significant association between A561C polymorphism and clinical activity was present. CONCLUSION: The sE-selectin, RF, and ESR, in addition to clinical indices, were associated with clinical activity in RA. We highlighted the presence of A/A genotype A561C polymorphism in our patients with RA.