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Introduction: Genetic variants that control dopamine have been associated with obesity in children through loss of control of satiety and impulses, the manifestation of addictive eating behaviors, and specific personality traits. The variants include FTO-rs9939609 and the MAO-A 30 pb u-VNTR low-transcription alleles (LTA). Objective: To evaluate the genetic association of FTO-rs9939609 and the MAO-A LTA, along with personality traits and eating behavior with obesity in Mayan children from Mexico. Methods: We cross-sectionally evaluated 186 children (70 with obesity and 116 with normal weight) 6-12 years old from Yucatan, Mexico. Nutritional status was defined with body mass index (BMI) percentiles. Personality traits were evaluated with the Conners and TMCQ tests; eating behavior was evaluated with the CEBQ test. Genotyping with real-time PCR and TaqMan probes was used for FTO-rs9939609, whereas PCR amplification was used for MAO-A u-VNTR. Results: High-intensity pleasure (p = 0.013) and moderate appetite (p = 0.032) differed according to nutritional status. Heterozygous FTO-rs9939609 T/A children showed higher mean scores of low-intensity pleasure (p = 0.002) and moderate appetite (p = 0.027) than homozygous T/T. Hemizygous boys having MAO-A LTA showed significantly higher mean scores of anxiety (p = 0.001) and impulsivity (p = 0.008). In multivariate models, only LTA alleles of MAO-A explained obesity in boys (OR = 4.44; 95% CI = 1.18-16.63). Conclusion: In the present study, MAO-A u-VNTR alleles were associated with obesity in multivariate models only in boys. These alleles might also have a role in personality traits such as anxiety and impulsivity, which secondly contribute to developing obesity in Mayan boys.

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Introduction: IFN-α is the main cytokine in SLE, and single nucleotide polymorphisms (SNP) in different genes could induce it. Aim: To determine the association of rs2004640 (IRF5), rs179008 (TLR7), rs1800795 (IL-6) and rs2280788 (CCL5) with SLE in Mexican women with Mayan ethnicity. Methods: DNA and RNA were isolated from the peripheral blood of 110 patients and 200 healthy control subjects. SNP genotyping and gene expression analysis of IRF5, TLR7, IL-6 and IFN-α were determined by real-time PCR and analyzed with SNP Stat, Stata 10.1 and Graph Pad Prism v5. Results: rs2004640, rs179008, and rs1800795 in both groups were according to Hardy-Weinberg equilibrium. Risk alleles rs179008T and rs2004640T frequencies were higher in controls (p = 0.015 and p = 0.028, respectively), whereas rs179008A frequency was higher in patients (p = 0.015). Allelic combination AGT frequency was higher in patients (p = 0.001). IL-6 rs1800795C > G and CCL5 rs2280788G > C frequencies did not show significant differences (p > 0.05), being rs2280788G (CCL5) monomorphic in controls. SLE patients showed higher TLR7, IRF5, IL6, and IFN-α mRNA levels. IRF5 expression was higher in SLE patients homozygous for rs2004640T (IRF5). Conclusion: This work showed the contribution of TLR7 and IRF5 in SLE pathogenesis in Mayan females from Yucatan.

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Background: L-2-hydroxyglutaric aciduria (L2HGA) is a rare inherited autosomal recessive neurometabolic disorder caused by pathogenic variants in the L2HGDH gene which encodes mitochondrial 2-hydroxyglutarate dehydrogenase. Here, we report a case of L2HGA in a Mexican-Mayan patient with a homozygous mutation at L2HGDH gene and clinical response to vitamin supplements and levocarnitine. Case report: A 17-year-old, right-handed female patient with long-term history of seizures, developmental delay and ataxia was referred to a movement disorders specialist for the evaluation of tremor. Her brain MRI showed typical findings of L2HGA. The diagnosis was corroborated with elevated levels of 2-hydroxyglutaric acid in urine and genetic test which revealed a homozygous genetic known variant c.569C>T in exon 5 of L2HGDH gene. She was treated with levocarnitine and vitamin supplements, showing improvement in tremor and gait. Discussion: To our knowledge this is the first report of a Mexican patient with L2HGA. This case adds information about a rare condition in a different ethnic group and supports the findings of other authors which encountered symptomatic improvement with the use of flavin adenine dinucleotide (and its precursor riboflavin), and levocarnitine. Highlights: We report the first case of Mexican-Mayan patient with L2HGA showing a missense homozygous mutation in L2HGDH gene, and improvement of symptoms with vitamin supplements and levocarnitine.

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Systemic Lupus Erythematosus (SLE) is an autoimmune disease in which genetic factors play a role in the susceptibility to develop it. Genes related to the synthesis of interferons such as TLR7 and genetics factors such as single nucleotide polymorphisms (SNPs) or copies number variation (CNV) in the gene have been involved with the development of the disease. The genetic differences between the populations contribute to the complexity of LES. Mexico has a mestizo population with a genetic load of at least three origins: Amerindian, Caucasian, and African. The mestizo of Yucatán is the only group whose contribution Amerindian is mainly Mayan, geographically distant from other Mexican Amerindians. We analyzed the CNV and the frequency of SNP rs179008 of the TLR7 as genetic risk factors in developing the disease in patients from Yucatán and Central Mexico. Results show that 14% of the cases of the Yucatecan population showed significantly >2 CNV and a higher risk of developing the disease (OR: 34.364), concerning 4% of those coming from Central Mexico (OR: 10.855). T allele and the A/T and T/T risk genotypes of rs179008 were more frequent in patients of Central Mexico than in those of Yucatán (50% vs. 30%, 93% vs. 30%, 4% vs. 1%), and association with susceptibility to develop SLE was observed (OR: 1.5 vs. 0.58, 9.54 vs. 0.66, 12 vs. 0.14). Data support the genetic differences between and within Mexican mestizo populations and the role of the TLR7 in the pathogenesis of SLE.

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OBJECTIVE: Genetic variants of PON1, rs70587, rs662, rs854560, GSTM1, and GSTT1 and two single nucleotide polymorphisms (SNP) at 9p21.3 locus, rs1333049, and rs2383207; were evaluated in association with the risk for premature coronary artery disease (CAD) in a population of Yucatan, Mexico. These genes are involved in the inactivation of pro-oxidants and pro-inflammatory mediators, lipid and xenobiotic metabolism, detoxification of reactive oxygen species, and regulation of cellular proliferation playing key roles in the pathogenesis of atherosclerosis. METHODS: We conducted a matched case-control study with 98 CAD cases and 101 healthy controls. Genotyping of PON1 and 9p21.2 SNP was performed by real time-PCR and for GSTM1 and GSTT1 with multiplex-PCR. Odds ratios (OR) were calculated to estimate association and generalized multifactor dimensionality reduction (GMDR) algorithm to identify gene-gene and gene-environment interactions. RESULTS: The distribution of all allele/genotype frequencies in controls was within Hardy-Weinberg expectations (p > .05) except for GSTM1. The allele/genotype frequencies of the GSTT1 null were significantly higher in CAD cases than in controls, suggesting association with higher risk for developing CAD. The other SNPs did not show any significant independent association with premature CAD. GMDR revealed a significant interaction between GSTT1 and LL55 genotype. Likewise, the body mass index (BMI) and smoking also showed an interaction with GSTT1. CONCLUSION: The GSTT1 null allele/genotype is associated with an increased risk of developing premature CAD, the effect of which is not modified by cardiovascular risk factors in the population of Yucatan.

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OBJECTIVES: High expression levels (HELs) of microRNA-122 (miR-122) or microRNA-222 (miR-222) have been associated with insulin resistance (IR), which leads to the development of obesity. The association between HELs of circulating miR-122 and miR-222 and the risk of obesity was evaluated in Mexican school-aged children, where childhood obesity is the primary cause of morbidity. METHODS: Anthropometric data, biochemical parameters, and caloric intake were obtained in 50 children with obesity and 49 children with normal weight. The expression of circulating miR-122 and miR-222 was measured by quantitative real-time polymerase chain reaction amplification. Data were analyzed using Student t test, Pearson correlation coefficient, associations with chi-square, and multiple linear and logistic regressions with SPSS software v.23. RESULTS: The mean relative expression for miR-122 and miR-222 was 0.33 and 5.65, respectively, for children with obesity and 0.22 and 3.16, respectively, for children with normal weight. The expression of miR-122 and miR-222 was 1.47 and 1.78-fold higher, respectively, in children with obesity (P = 0.001 and P = 0.025). HELs of both miR-122 and miR-222 were associated with body mass index (BMI), waist to height ratio (WHR), fat percentage, serum high-density lipid levels, triglycerides (TGs), and metabolic index (MI) (P < .001). CONCLUSIONS: The HELs of circulating miR-122 conferred a 3.85-fold increase in the risk for obesity, whereas the HELs of both miR-122 and miR-222 conferred a 3.11-fold increase in the risk for obesity, which were also associated with higher anthropometric or biochemical parameters, such as BMI, WHR, fat percentage, serum high-density lipid levels, TGs, and MI, in Mayan children.

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This article was published online with an error. Given names and family names of the authors were interchanged. The correct author names are presented above. The original article has been corrected.

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We report one complex paternity case presenting a presumable paternal four-step STR mutation between the alleged father (AF) and child; the complexity of the case required the AF-brother hypothesis to be discarded without including this DNA sample. A total of 23 autosomal STR loci included in the Powerplex Fusion® and Globalfiler™ kits confirmed one isolated mismatch for D22S1045 between the AF (17/17) and the male child (13/15) in the presence of the mother (15/15). In this case, the STR structure and father's age do not seem to have contributed to promote the observed multistep mutation. The Paternity Index (PI) based on 23 autosomal STRs did not favor the AF paternity over the AF-brother hypothesis based on a flat prior (PI = 0.1217; W = 10.85%). For that reason, we included 38 autosomal human identification (HID) insertions-deletions (indels) and 20 retrotransposon insertion polymorphisms (RIPs) contained in the InnoTyper® 21 kit. Although these biallelic markers favored the AF paternity rather than the AF-brother hypothesis (LR = 110.3; W = 99.1%), the global PI based on 81 autosomal markers supported moderately the AF paternity hypothesis (LR = 13.4; W = 93.1%). The application of different mutation models showed a consistent support to the AF paternity hypothesis (PI = 93.1-99.95%), which could be useful for interpretation in these multistep STR mutation cases. In brief, we showed the impact of a four-step mutation at D22S1045 to obtain definitive paternity conclusions, particularly under a complex scenario when the AF-brother hypothesis is assessed. Forensic genomics arises as the next option for similar complex paternity cases.

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OBJECTIVES: Genetic variation of the fat mass and obesity associated gene (FTO) has been identified as a risk factor for obesity and obesity traits. Distribution of FTO single nutleotide polymorphisms (SNPs) rs1421085T>C, rs9939609T>A, rs8057044G>A and copy number variation (CNV) was evaluated in association with childhood obesity or overweight status in children with Mayan ethnicity. METHODS: We included 318 school-aged children with obesity or overweight status (body mass index [BMI]: >85th percentile) and 303 children with normal weight (BMI: 15th-85th percentile). Genotyping was performed using real-time polymerase chain reaction (RT-PCR) with TaqMan probes. The cross-sectional study was carried out using univariate and multivariate logistic regression models adjusted for gender. RESULTS: FTO-SNP rs1421085 showed significant differences between children with obesity and children with normal weight for the heterozygous genotype (P = 0.003) and for allele frequencies (P = 0.023). Adjusting by gender, significant differences were found in frequencies of the hetezygous genotype of SNPs rs9939609 (P = 0.023) and rs1421085 (P = 0.003) as well as in allele frequencies (P = 0.042 and P = 0.013, respectively) between girls with obesity and girls without obesity. In contrast, SNP rs8057044 was significantly different only between heterozygous overweight versus normal weight boys (P = 0.035) and for the allele frequency of rs8057044 (P = 0.021). The mean relative CNV was significantly higher in male overweight children than in boys with normal weight (P = 0.000). CONCLUSIONS: The FTO SNP rs1421085 is a genetic factor associated with obesity in Mayan school-aged children. FTO SNPs rs1421085 and rs9939609 affect genetic susceptibility for obesity only in girls, whereas, SNP rs8057044 and CNV are associated with overweight status only in boys.

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Resumen Introducción Las mutaciones, del E746-A750 exón 19 y L858R exón 21 del gen EGFR en células tumorales de CPNM representan biomarcadores de respuesta a fármacos inhibidores de tirosina cinasa (ITK). Pacientes con tumores positivos a mutaciones EGFR muestran mejor respuesta y mayor sobrevivencia. Estas mutaciones ocupan el 90% de las mutaciones en cáncer de pulmón. Objetivo Evaluar la frecuencia de las mutaciones del E746-A750 exón 19 y L858R exón 21 del EGFR en muestras de biopsia de CPNM y en muestras de suero de población abierta de Yucatán. Material y métodos Se seleccionaron 19 muestras de biopsia de CNPM tipo adeconocarcinoma y 101 sueros de sujetos sanos. Las mutaciones del E746-A750 y L858R en EGFR se determinaron mediante amplificación por PCR oligo-alelo específica (PCR-ASO). Se calcularon las frecuencias genotípicas y alélicas y su distribución según Hardy Weinberg, utilizando la plataforma SNPstats. Resultados En muestras de suero se determinó el genotipo homocigoto (1/1) en 26.58%, 73.42% el heterocigoto (1/0) y ausencia del genotipo mutante con deleción (0/0) para del E746-A750; en tanto que, para L858R, 21.78% resultó homocigoto (TT), 54.46% heterocigoto (T/G) y 23.76% mutantes GG. En las biopsias, el heterocigoto fue más frecuente en ambas mutaciones 63.16% y 73.68% para del E746-A750 y L858R, respectivamente. Conclusión. La frecuencia de las mutaciones del gen EGFR en las muestras de sueros fue de 36.71% para la deleción del E746-A750 en exón 19 y 50.99% para L858R en exón 21. La distribución de las mutaciones en muestras de biopsia CPNM resultó en 42.11% para cada mutación estudiada.

Abstract Introduction EGFR mutations, del E746-A750 in exon 19 and L858R in exon 21 in tumor cells of NMLC represent biomarkers of response to tyrosine kinase inhibitors (TKI) therapy. Patients with tumors positive for EGFR mutations show better response and greater survival. These mutations occupy 90% of mutations in lung cancer. Objective To evaluate the frequency of mutations del E746-A750-exon 19 and L858R-exon 21 of EGFR gene in NMLC biopsy samples and in serum samples of the general population from Yucatán. Material and methods 19 NMLC biopsy samples of adenocarcinoma type and 101 serum samples from healthy subjects were selected. EGFR mutations del E746-A750 and L858R were determined by allele-specific PCR amplification (PCR-ASO). The genotypic and allelic frequencies; and their distribution according to Hardy Weinberg expectations were calculated using the SNPstats software. Results For serum, EGFR del E746-A750 mutation, homozygous genotype (1/1) was present in 26.58%, heterozygote (1/0) in 73.42% and absence of mutant genotype with deletion (0/0); whereas for L858R mutation, 21.78% were homozygous (TT), 54.46% heterozygous (T/G) and 23.76% GG mutants. For the NMLC biopsies, the heterozygote was the most frequent genotype for both mutations, 63.16% and 73.68% for del E746-A750 and L858R, respectively. Conclusion The frequency of mutations of EGFR gene in serum samples was 36.71% for deletion delE746-A750 in exon 19 and 50.99% for L858R in exon 21. Distribution of mutations in biopsy samples NMLC resulted in 42.11% for each EGFR mutation.