Biomarkers in Systemic Lupus Erythematosus along with Metabolic Syndrome.

Metabolic syndrome (MetS) is a group of physiological abnormalities characterized by obesity, insulin resistance (IR), and hypertriglyceridemia, which carry the risk of developing cardiovascular disease (CVD) and type 2 diabetes (T2D). Immune and metabolic alterations have been observed in MetS and are associated with autoimmune development. Systemic lupus erythematosus (SLE) is an autoimmune disease caused by a complex interaction of environmental, hormonal, and genetic factors and hyperactivation of immune cells. Patients with SLE have a high prevalence of MetS, in which elevated CVD is observed. Among the efforts of multidisciplinary healthcare teams to make an early diagnosis, a wide variety of factors have been considered and associated with the generation of biomarkers. This review aimed to elucidate some primary biomarkers and propose a set of assessments to improve the projection of the diagnosis and evolution of patients. These biomarkers include metabolic profiles, cytokines, cardiovascular tests, and microRNAs (miRs), which have been observed to be dysregulated in these patients and associated with outcomes.

Breastfeeding Practices and Postpartum Depression in Mexican Women during the COVID-19 Pandemic: A Cross-Sectional Study.

Background: Breastfeeding is a characteristic process of mammals that ensures delivery of an adequate nutritional supply to infants. It is the gold standard food source during an infant's first months of life. Since the onset of the COVID-19 pandemic in 2020, people in quarantine have experienced a wide range of feelings, which may make isolation challenging in terms of maternal health. This study focused on the prevalence of breastfeeding practices and postpartum depression (PPD) among Mexican women during the COVID-19 pandemic. Materials and Methods: This cross-sectional study included 586 postpartum women who completed an online survey 4-8 weeks after delivery from April to December 2020 in Guadalajara, Mexico. The aim was to identify potentially depressed mothers according to the Edinburgh Postnatal Depression Scale (EPDS) and describe their breastfeeding practices. Results: The mean maternal age was 30.4 ± 4.6 years, the mean EPDS score was 9.6 ± 5.0, and the PPD prevalence according EPDS scores was 27.1%. Exclusive breastfeeding (EBF) was reported by 32.3% of mothers in the first 48 h and by 70.3% of mothers 48 h after delivery. EBF was associated with a lower prevalence of PPD during the first 48 h (p = 0.015) and after the first 48 h (p = 0.001) after delivery. Skin-to-skin contact (SSC) was reported by 385 (65.7%) mothers. PPD was less frequent in mothers practicing SSC (20.3%) than it was in those not practicing SSC (40.3%) (p = 0.001). A higher percentage of mothers practiced SSC breastfed (66.9%) and used EBF (150, 79.4%) (p = 0.012 and 0.001, respectively). Conclusions: Results suggest that the pandemic emergency and restrictions imposed on the population significantly affected the well-being of mothers after birth, and that these effects may have posed risks to the mental health and emotional stability of postpartum mothers. Therefore, encouraging BF or EBF and SSC may improve or limit depressive symptoms in postpartum mothers.

Long COVID-19 and Insulin Autoimmune Syndrome: A Case Report.

PURPOSE: To describe a case report of a patient with symptoms associated with metabolic alterations 1 month after having COVID-19. METHODS: Laboratory tests, clinical evaluations, and body composition assessments were performed by specialists. FINDINGS: The patient presented excessive sweating, hot flashes, dizziness, blurred vision, and seizure. Laboratory tests indicated low glucose levels after convulsions (50, 42.7, and 55 mg/dL), high insulin levels (basal, 638 µIU/mL; 2-hour, >1000 µU/mL), and positivity for anti-insulin antibodies. The patient was diagnosed with insulin autoimmune syndrome. Treatment with azathioprine and nutritional recommendations improved remission. IMPLICATIONS: SARS-CoV-2 infection or vaccination might induce insulin tolerance failure.

Osteopontin: A Bone-Derived Protein Involved in Rheumatoid Arthritis and Osteoarthritis Immunopathology.

Osteopontin (OPN) is a bone-derived phosphoglycoprotein related to physiological and pathological mechanisms that nowadays has gained relevance due to its role in the immune system response to chronic degenerative diseases, including rheumatoid arthritis (RA) and osteoarthritis (OA). OPN is an extracellular matrix (ECM) glycoprotein that plays a critical role in bone remodeling. Therefore, it is an effector molecule that promotes joint and cartilage destruction observed in clinical studies, in vitro assays, and animal models of RA and OA. Since OPN undergoes multiple modifications, including posttranslational changes, proteolytic cleavage, and binding to a wide range of receptors, the mechanisms by which it produces its effects, in some cases, remain unclear. Although there is strong evidence that OPN contributes significantly to the immunopathology of RA and OA when considering it as a common denominator molecule, some experimental trial results argue for its protective role in rheumatic diseases. Elucidating in detail OPN involvement in bone and cartilage degeneration is of interest to the field of rheumatology. This review aims to provide evidence of the OPN's multifaceted role in promoting joint and cartilage destruction and propose it as a common denominator of AR and OA immunopathology.

Osteopontin: another piece in the systemic lupus erythematosus immunopathology puzzle.

Osteopontin (OPN) is a phosphoglycoprotein involved in bone remodelling, wound healing, cell adhesion, tissue remodelling, and immune response that is distributed widely in normal adult tissues. OPN biological activity is regulated by thrombin and matrix metalloproteinases (MMPs) cleavage, where the full-length (OPN-FL) protein and the cleaved OPN-N are associated with autoimmune diseases such as systemic lupus erythematosus (SLE). OPN overexpression has been associated with a predisposition to SLE and bad prognosis since OPN could mediate a sustained polyclonal B cell activation that besides to intracellular OPN (iOPN) form, promote the T follicular helper (TFH) cells and enhance anti-nuclear antibody production. Currently, the role of OPN in lupus nephritis (LN) has been reported and extensively studied; however, no data are available about the potential mechanism of OPN in neuropsychiatric SLE (NPSLE). In this review, we highlighted the contribution of OPN and iOPN in LN and NPSLE immunopathology.

The DNA co-vaccination using Sm antigen and IL-10 as prophylactic experimental therapy ameliorates nephritis in a model of lupus induced by pristane.

INTRODUCTION: Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies such as anti-Sm. Studies in patients with SLE and murine models of lupus reveal that the most critical anti-Sm autoantibodies are predominantly direct against D1(83-119), D2, and B´/B epitopes. OBJECTIVES: The present study aimed to analyze the induction of antigen-specific tolerance after prophylactic immunization with a DNA vaccine encoding the epitopes: D183-119, D2, B´/B, and B´/BCOOH in co-vaccination with IFN-γ or IL-10 in a murine model of lupus induced by pristane. MATERIAL AND METHODS: To obtain endotoxin-free DNA vaccines, direct cloning techniques using pcDNA were performed: D183-119, D2, B´/B, B´/BCOOH, IFN-γ, or IL-10. Lupus was induced by 0.5 mL of pristane via intraperitoneal in BALB/c female mice. Immunoprecipitation with K562 cells was metabolically labeled with 35S and ELISA to detect serum antibodies or mice IgG1, IgG2a isotypes. ELISA determined IL-10 and IFN-γ from splenocytes supernatants. Proteinuria was assessed monthly, and lupus nephritis was evaluated by immunofluorescence, and electron microscopy. RESULTS: The prophylactic co-vaccination with D2/IL-10 reduced the expression of kidney damage observed by electron microscopy, direct immunofluorescence, and H & E, along with reduced level of anti-nRNP/Sm antibodies (P = 0.048). CONCLUSION: The prophylactic co-vaccination of IL-10 with D2 in pristane-induced lupus ameliorates the renal damage maybe by acting as prophylactic DNA tolerizing therapy.

Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico / Contribución del polimorfismo rs3211938 de CD36 a los niveles de glucosa, las lipoproteínas de baja densidad oxidadas, la resistencia a la insulina y el índice de masa corporal en mestizos mexicanos con diabetes de tipo 2 del occidente de México

Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p < 0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p < 0.05 and p < 0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p < 0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p < 0.001; p < 0.001; p < 0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico. (AU)

Antecedentes: la diabetes mellitus de tipo 2 (DMT2) es un trastorno metabólico crónico caracterizado por hiperglucemia, resistencia a la insulina (RI) y metabolismo anormal de ácidos grasos en el que se ha implicado el receptor CD36 en la disregulación de la glucosa y los lípidos. Objetivo: evaluar la contribución del polimorfismo CD36 rs3211938 al perfil metabólico en individuos mestizos mexicanos con DMT2 del occidente de México. Métodos: se incluyeron 115 individuos clasificados en adultos sin DMT2 (NDMT2) y pacientes con DMT2. El polimorfismo CD36 rs3211938 se identificó mediante PCR-RFLP. Las mediciones antropométricas y metabólicas se realizaron mediante métodos de rutina y la insulina y las LDL-oxidadas (LDL-ox) se midieron por ELISA. Resultados: las distribuciones de los genotipos entre los pacientes NDMT2 y DMT2 fueron diferentes (p < 0,001), así como la frecuencia alélica (p = 0,002). Los individuos NDMT2 portadores del genotipo TG mostraron niveles más bajos de insulina basal e índice HOMA-IR en comparación con los portadores del genotipo TT (p < 0,05 y p < 0,05, respectivamente). En el grupo DMT2, los portadores del genotipo TG presentaron valores elevados de índice de masa corporal (IMC), índice cintura-cadera (ICC) y peso (p = 0,001; p < 0,05 y p < 0,05, respectivamente) y niveles más altos de glucosa basal, HDL-colesterol, LDL-ox y HOMA-IR (p < 0,001; p < 0,001; p < 0,001 y p = 0,001, respectivamente) en comparación con los portadores del genotipo TT. Conclusión: el genotipo TG del polimorfismo CD36 rs3211938 se asocia a altos niveles de glucosa, ox-LDL, HDL-colesterol y RI, y a aumentos del IMC en los pacientes mestizos mexicanos con DMT2 del occidente de México. (AU)

Contribution of rs3211938 polymorphism at CD36 to glucose levels, oxidized low-density lipoproteins, insulin resistance, and body mass index in Mexican mestizos with type-2 diabetes from western Mexico.

INTRODUCTION: Background: type-2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance (IR), and abnormal fatty acid metabolism in which the CD36 receptor has been implicated in glucose and lipid dysregulation. Objective: to evaluate the contribution of polymorphism CD36 rs3211938 to metabolic profile in T2DM Mexican mestizos from western Mexico. Methods: we included 115 individuals classified as non-T2DM (NT2DM) adults and T2DM patients. Polymorphism CD36 rs3211938 was assessed by PCR-RFLP. Anthropometric and metabolic markers were measured by routine methods, and insulin and oxidized LDL (ox-LDL) were measured by ELISA. Results: the distribution of genotypes between NT2DM and T2DM patients was different (p < 0.001), as was the allele frequency (p = 0.002). NT2DM TG carriers showed the lowest levels of basal insulin and HOMA-IR index in comparison with TT carriers (p < 0.05 and p < 0.05, respectively). In the T2DM group TG carriers showed high BMI, WHR, and weight values (p = 0.001; p ≤ 0.05 and p < 0.05, respectively), and the highest levels of basal glucose, HDL-cholesterol, ox-LDL, and HOMA-IR (p < 0.001; p < 0.001; p < 0.001, and p = 0.001, respectively) in comparison with diabetic TT carriers. Conclusion: the CD36 rs3211938 TG genotype is associated with high levels of glucose, ox-LDL, HDL-cholesterol, and IR, and with increased BMI in Mexican mestizo T2DM patients from western Mexico.

INTRODUCCIÓN: Antecedentes: la diabetes mellitus de tipo 2 (DMT2) es un trastorno metabólico crónico caracterizado por hiperglucemia, resistencia a la insulina (RI) y metabolismo anormal de ácidos grasos en el que se ha implicado el receptor CD36 en la disregulación de la glucosa y los lípidos. Objetivo: evaluar la contribución del polimorfismo CD36 rs3211938 al perfil metabólico en individuos mestizos mexicanos con DMT2 del occidente de México. Métodos: se incluyeron 115 individuos clasificados en adultos sin DMT2 (NDMT2) y pacientes con DMT2. El polimorfismo CD36 rs3211938 se identificó mediante PCR-RFLP. Las mediciones antropométricas y metabólicas se realizaron mediante métodos de rutina y la insulina y las LDL-oxidadas (LDL-ox) se midieron por ELISA. Resultados: las distribuciones de los genotipos entre los pacientes NDMT2 y DMT2 fueron diferentes (p < 0,001), así como la frecuencia alélica (p = 0,002). Los individuos NDMT2 portadores del genotipo TG mostraron niveles más bajos de insulina basal e índice HOMA-IR en comparación con los portadores del genotipo TT (p < 0,05 y p < 0,05, respectivamente). En el grupo DMT2, los portadores del genotipo TG presentaron valores elevados de índice de masa corporal (IMC), índice cintura-cadera (ICC) y peso (p = 0,001; p < 0,05 y p < 0,05, respectivamente) y niveles más altos de glucosa basal, HDL-colesterol, LDL-ox y HOMA-IR (p < 0,001; p < 0,001; p < 0,001 y p = 0,001, respectivamente) en comparación con los portadores del genotipo TT. Conclusión: el genotipo TG del polimorfismo CD36 rs3211938 se asocia a altos niveles de glucosa, ox-LDL, HDL-colesterol y RI, y a aumentos del IMC en los pacientes mestizos mexicanos con DMT2 del occidente de México.

CCR2/CCL2 and CMKLR1/RvE1 chemokines system levels are associated with insulin resistance in rheumatoid arthritis.

Rheumatoid arthritis (RA) has been associated with insulin resistance (IR). Due to an excess in storage of white adipose tissue, IR has an inflammatory process that overlaps with RA. This is performed by the activation/migration of monocytes carried out by the CCR2/CCL2 and CMKLR1/RvE1 chemokines systems. Furthermore, these can potentiate chronic inflammation which is the central axis in the immunopathogenesis of RA. We evaluated the association between the relative expression of CCR2 and CMKLR1 and the serum levels of their ligands CCL2 and RvE1, in the context of adiposity status with IR as a comorbidity in RA. We studied 138 controls and 138 RA-patients classified with and without IR. We evaluated adiposity, RA activity, IR status and immunometabolic profiles by routine methods. Insulin, CCL2 and RvE1 serum levels were determined by ELISA. Relative expression of CCR2, CMKLR1 and RPS28 as constitutive gene by SYBR green RT-qPCR and 2-ΔΔCT method. Increased measurements were observed of body adiposity and metabolic status as follows: RA with IR>control group with IR>RA without IR> control group without IR. CCR2 and CMKLR1 relative expression was increased in RA without IR versus control without IR. CCR2: 2.3- and 1.3-fold increase and CMKLR1: 3.5- and 2.7-fold increase, respectively. Whereas, CCR2 expression correlates with CMKLR1 expression (rho = 0.331) and IR status (rho = 0.497 to 0.548). CMKLR1 expression correlates with inflammation markers (rho = 0.224 to 0.418). CCL2 levels were increased in the RA groups but levels of RvE1 were increased in RA without IR. We conclude that in RA with IR, the chemokine receptors expression pattern showed a parallel increase with their respective ligands. RA and IR in conjunction with the pathological distribution of body fat mass might exacerbate chronic inflammation. These results suggest that high CCL2 levels and compensatory RvE1 levels might not be enough to resolve the inflammation by themselves.

Downregulation of hippocampal NR2A/2B subunits related to cognitive impairment in a pristane-induced lupus BALB/c mice.

Neuropsychiatric systemic lupus erythematosus (NPSLE) is associated with learning and memory deficit. Murine model of lupus induced by pristane in BALB/c mice is an experimental model that resembles some clinical and immunological SLE pathogenesis. Nevertheless, there is no experimental evidence that relates this model to cognitive dysfunction associated with NR2A/2B relative expression. To evaluate cognitive impairment related to memory deficits in a murine model of lupus induced by pristane in BALB/c mice related to mRNA relative expression levels of NR2A/2B hippocampal subunits in short and long-term memory task at 7 and 12 weeks after LPS exposition in a behavioral test with the use of Barnes maze. A total of 54 female BALB/c mice 8-12 weeks old were included into 3 groups: 7 and 12 weeks using pristane alone (0.5 mL of pristane) by a single intraperitoneal (i.p.) injection. A control group (single i.p. injection of 0.5 mL NaCl 0.9%) and pristane plus LPS exposure using single i.p. pristane injection and LPS of E. coli O55:B5, in a dose of 3mg/kg diluted in NaCl 0.9% 16 weeks post-pristane administration. To determine cognitive dysfunction, mice were tested in a Barnes maze. Serum anti-Sm antibodies and relative expression of hippocampal NR2A/2B subunits (GAPDH as housekeeping gene) with SYBR green quantitative reverse transcription polymerase chain reaction and 2-ΔΔCT method were determined in the groups. Downregulation of hippocampal NR2A subunit was more evident than NR2B in pristane and pristane+LPS at 7 and 12 weeks of treatment and it is related to learning and memory disturbance assayed by Barnes maze. This is the first report using the murine model of lupus induced by pristane that analyzes the NMDA subunit receptors, finding a downregulation of NR2A subunit related to learning and memory disturbance being more evident when they were exposed to LPS.

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.

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.