COMT and SCN9A gene variants do not contribute to chronic low back pain in Mexican-Mestizo patients.

BACKGROUND: Chronic low back pain (CLBP) is a complex condition in which genetic factors play a role in its susceptibility. Catechol-O-methyltransferase (COMT) and sodium channel NaV1.7 (SCN9A) genes are implicated in pain perception. The aim is to analyze the association of COMT and SCN9A with CLBP and their interaction, in a Mexican-Mestizo population. METHODS: A case-control study was conducted. Cases corresponded to adults of both sexes with CLBP. Controls were adults with no CLBP. Variants of SCN9A and COMT were genotyped. Allelic and genotypic frequencies and Hardy-Weinberg equilibrium (HWE) were calculated. Association was tested under codominant, dominant, and recessive models. Multifactor dimensionality reduction was developed to detect epistasis. RESULTS: Gene variants were in HWE, and there was no association under different inheritance models in the whole sample. In women, in codominant and dominant models, a trend to a high risk was observed for AA of rs4680 of COMT (OR = 1.7 [0.5-5.3] and 1.6 [0.7-3.4]) and for TT of rs4633 (OR = 1.6 [0.7-3.7] and 1.6 [0.7-3.4]). In men, a trend to low risk was observed for AG genotype of rs4680 in the same models (OR = 0.6 [0.2-1.7] and 0.7 [0.3-1.7]), and for TC genotype of rs4633 in the codominant model (OR = 0.6 [0.2-1.7]). In the interaction analysis, a model of the SCN9A and COMT variants showed a CVC of 10/10; however, the TA was 0.4141. CONCLUSION: COMT and SCN9A variants are not associated with CLBP in the analyzed Mexican-Mestizo population.

Epistasis Between Two Gene Variants of Leptin and Vascular Endothelial Growth Factor Genes in the Development of Primary Knee Osteoarthritis.

BACKGROUND: The association of leptin (LEP) and vascular endothelial growth factor A (VEGFA) genes with the susceptibility to knee osteoarthritis (OA) has been analyzed; however, the epistasis between them has not been investigated. OBJECTIVE: The objective of the study was to analyze the association of LEP and VEGFA variants and their interaction with primary knee OA in a Mexican Mestizo population. METHODS: A case-control study was developed. Cases were ≥40 years, BMI ≤27 kg/m2, with primary knee OA and radiologic Grade ≥2. Controls were participants with no knee OA and a radiologic Grade < 2. The rs2167270 of LEP and rs2010963 of VEGFA were genotyped. Genotypic association was tested under codominant, dominant, and recessive models. Uni- and multi-variate analyses were developed through non-conditional logistic regression. The multifactor dimensionality reduction algorithm was developed to detect epistasis. RESULTS: Participants comprised 103 cases and 179 controls. Allelic and genotypic distributions did not show differences between the groups. Notwithstanding, a statistically significant interaction was observed between the LEP and VEGFA genes (p = 0.02) with a testing accuracy of 0.5199 and cross-validation consistency of 10/10. This interaction model confers an increased risk to knee OA (OR [95% CI] = 1.8 [1.1-2.9]). CONCLUSION: Interaction between LEP and VEGFA is related with genetic susceptibility to developing primary knee OA.

Are functional variants of the microRNA-146a gene associated with primary knee OA? Evidence in Mexican mestizo population.

MicroRNA-146a (miR-146a) is an inflammatory response regulator whose expression is deregulated in osteoarthritis (OA); variations in the miR-146a gene could affect OA risk. This study aimed to analyze the association between two functional variants of the miR-146a gene and primary knee OA in Mexican mestizo population. Methods and Results. A case-control study was conducted with cases defined as individuals aged ≥ 40 years with primary knee OA grade ≥ 2, according to the Kellgren-Lawrence system. Controls were volunteers with no primary knee OA with radiographic grade < 2. TaqMan allelic discrimination assays genotyped the rs2910164 and rs57095329. Allelic and genotypic frequencies, as well as the Hardy-Weinberg equilibrium (HWE), were calculated. The genetic association was tested under codominant, dominant, and recessive models. Non-conditional logistic regressions were carried out to estimate the association magnitude. We included 310 cases and 379 controls. Despite rs2910164 being in HWE, there was no association under codominant, dominant, and recessive models. In women with OA grade 2, the codominant model found a trend between the CC genotype and increased risk [OR (95% CI) 1.6 (0.7-3.5)]; the same trend was found in OA grade 4 in the codominant and recessive models [1.8 (0.6-5.4) and 2.0 (0.7-5.9)]. Conversely, in men with OA grade 4, the CC genotype tended to be associated with a lower risk in the codominant and recessive models [0.6 (0.1-6.0) and 0.5 (0.1-5.1)]. Conclusion. Our results show that miR-146a gene variants are not significantly associated with primary knee OA in Mexican mestizos.

DNA methyltransferase genes polymorphisms are associated with primary knee osteoarthritis: a matched case-control study.

DNA methylation is an epigenetic mechanism involved in the development of primary osteoarthritis (OA). The association between DNA methyltransferases (DNMTs) genes polymorphisms and diseases in which DNA methylation plays a role in their pathogenesis has been described (e.g., cancer); however, its relationship with OA has not been investigated. The aim of this study was to analyze the association between DNMT1, DNMT3A, and DNMT3B polymorphisms with radiologic primary knee OA in Mexican mestizo population. A matched case-control study was conducted (ratio, 1:1). Cases included 244 subjects with definite radiographic knee OA (grade ≥ 2). Controls were matched by age and gender and were subjects with no definite radiographic knee OA/normal (grade < 2). The DNMTs polymorphisms were genotyped by TaqMan allelic discrimination assays. Conditional logistic regression was carried out, and the genetic association was tested under co-dominant, dominant, and recessive inheritance models. Haplotypes for DNMT1 polymorphisms were constructed and their associations were also tested. The CC genotypes of rs2228611 and rs2228612 of DNMT1 were associated with a lower risk for primary knee OA under a co-dominant and a recessive model [OR (95% CI) 0.4 (0.2-0.8)/0.5 (0.3-0.8) and 0.3 (0.1-0.8)/0.3 (0.1-0.7), respectively]. The CT haplotype of DNMT1 polymorphisms was associated with a lower risk [OR (95% CI) 0.71 (0.51-0.97)]. The CC genotype of rs2424913 of DNMT3B was associated with an increased risk under a co-dominant and a dominant model [OR (95% CI) 3.0 (1.1-8.0), and 1.6 (1.1-2.4), respectively]. Our results show that DNMTs polymorphisms are associated with primary knee OA.

The impact of body mass index and central obesity on the spino-pelvic parameters: a correlation study.

INTRODUCTION: Obesity is an increasing problem of epidemic proportion, and it is associated with various musculoskeletal disorders, including impairment of the spine. However, the relationship between obesity and spino-pelvic parameters remains to date unsupported by an objective measurement of the mechanical behavior of the spino-pelvic parameters depending on body mass index (BMI) and the presence of central obesity. Such analysis may provide a deeper understanding of this relationship. PURPOSE: To assess whether BMI and central obesity are associated with modifications on spino-pelvic parameters and determine if exists any correlation between BMI and obesity with the type of lumbar lordosis (LL). METHODS: A cross-sectional study with 200 participants was conducted. Parameters measured were LL, pelvic tilt, sacral slope, and pelvic incidence (PI), using lumbosacral radiographs in lateral view. Subjects were classified depending on BMI. In a secondary analysis, the subjects were categorized into two groups depending on the presence or not of elevated abdominal circumference. The categorical variables were compared using Chi-square test, and the mean values were compared using ANOVA and student t test. A Spearman correlation test was used to analyze the correlation between BMI categories and LL types. RESULTS: From the total of participants, there were 51 (25.5 %) normal weight subjects, 93 (46.5 %) overweight, and 56 (28 %) obese individuals. The spino-pelvic parameters among these groups are practically equal. The correlation between the different BMI categories and LL types is poor 0.06 (P = 0.34). In a secondary analysis, grouping the participants in obese and non-obese, the results showed that obesity is modestly positively associated with increasing of spino-pelvic parameters values, in particular with PI (P = 0.078). The comparison made between the presence or not of central obesity, interestingly did not show significant differences. CONCLUSIONS: Despite the results did not reach statistically significant differences, the results indicate that the obese spine is slightly different from the non-obese spine. Therefore, this relationship deserves future attention.

Genetic association analysis of Osteopontin and Matrix Gla Protein genes polymorphisms with primary knee osteoarthritis in Mexican population.

Primary osteoarthritis (OA) is a complex entity in which several loci related to different molecular pathways or classes of molecules are associated with its development as demonstrated through genetic association studies. Genes involved in bone formation and mineralization, such as osteopontin (OPN) and Matrix Gla protein (MGP), could also be related with OA. The aim of this study was to evaluate the association between the genetic variants of OPN and MGP with primary knee osteoarthritis in a Mexican population. A case-control study was conducted in 296 patients with primary knee osteoarthritis and in 354 control subjects. Study groups were assessed radiologically. The rs11730582 of OPN and rs1800802, rs1800801, and rs4236 of MGP were determined by TaqMan allele discrimination assays. The haplotypes of the polymorphisms of MGP were constructed. The association was tested through univariate and multivariate non-conditional logistic regression analyses. The polymorphisms of MGP complied with Hardy-Weinberg (HW) equilibrium. The polymorphisms of OPN and MGP were not significantly associated with primary knee osteoarthritis in the codominant, dominant, and recessive models (p > 0.05). Our study suggests that there are no associations between OPN and MGP polymorphisms with primary knee osteoarthritis in Mexican population.

Vitamin D receptor gene polymorphisms and susceptibility for primary osteoarthritis of the knee in a Latin American population.

BACKGROUND: Primary Osteoarthritis (OA) of the knee is a multifactorial disease that has an important genetic component, and several genes have been associated with its development. The vitamin D receptor has a role in skeletal metabolism that suggests a relationship with OA. The aim of this study was to analyze the association of Vitamin D receptor gene (VDR) polymorphisms in Mexican Mestizo patients. METHODS: A case-control study was conducted in which 107 cases with primary OA of the knee and 114 controls were included. Cases were patients > 40 years of age with a Body mass index (BMI) of ≤27 and a radiological score for OA of the knee of ≥2. Controls were subjects > 40 years of age with a radiological score of < 2. VDR polymorphisms rs1544410, rs7975232, and rs731236 were analyzed by means of restriction endonucleases, and logistic regression was developed to evaluate risk magnitude. RESULTS: A significantly increased risk was found of nearly two-fold for the allele T and TT genotypes of rs731236, independently of other well recognized risk factors. CONCLUSIONS: The rs731236 polymorphism is associated with the risk of primary OA of the knee in Mexican Mestizo population.

Síndrome de Rett: resonancia magnética de cráneo, y radiografía simple de manos y pies / Rett syndrome: finding in MR cranial imaging and simple radiography of hands and feet

Antecedentes: el síndrome de Rett es un trastorno del neurodesarrollo que afecta casi exclusivamente a mujeres, asociado con discapacidad cognitiva y motora severas. En ausencia de marcadores biológicos, el diagnóstico se determina con base en criterios clínicos. Además, se ha informado de algunas anormalidades del sistema óseo; no se han descrito en el cráneo óseo.Objetivo: describir cualitativamente los hallazgos estructurales del encéfalo obtenidos por resonancia magnética de cráneo, así como las alteraciones óseas identificadas por radiografías simples de manos y pies.Material y métodos: cinco pacientes afectadas por síndrome de Rett, con edades de 4.9 a 10.2 años (media de 8.3). Criterios de inclusión: diagnóstico de síndrome de Rett formulado con base en criterios clínicos aceptados. En todas se contó con el consentimiento informado de los padres. Se les realizó examen clínico neurológico, resonancia magnética de cráneo, convencional y con gadolinio, utilizando equipo Magneton 1.5-Tesla (Gyroscan S 15 Siemens), con técnica espín-eco y cortes sagitales, coronales y axiales (el espesor del corte fue de 5 mm); y radiografía simple de manos y pies.Resultados: por resonancia magnética se halló aumento en grosor del diploe, atrofia de la sustancia gris cerebral, atrofia moderada de sustancia blanca, adelgazamiento del cuerpo calloso, alteración en mesencéfalo y fosa posterior, dilatación severa de cisterna prebulbar y prepontina, hipotrofia moderada del vermis superior y cuarto ventrículo asimétrico. Los hallazgos en imágenes de radiografías simples de manos y pies consistieron en acortamiento de cuarto meta-carpiano bilateral, del quinto metacarpiano uni y bilateral, reducción del cuarto metatarsiano en forma bilateral y pies hipotróficos.Conclusiones: las alteraciones en cráneo, estructura del encéfalo y alteraciones óseas en manos y pies son hallazgos fenotípicos que constituyen herramientas adicionales para el diagnóstico temprano y la estadificación del síndrome de Rett.