Association of NFκß, TNFα, IL-6, IL-1ß, and LPL Polymorphisms with Type 2 Diabetes Mellitus and Biochemical Parameters in a Mexican Population.

Chronic low-grade inflammation is strongly related to the etiology of diabetes mellitus type 2 (T2DM), and the expression of inflammatory cytokines may be modulated by polymorphisms located in the regulatory regions of the NFκß, IL-1ß, IL-6, TNFα, and LPL genes. We considered it particularly important to investigate the relationship of gene polymorphisms involved in chronic inflammation with the risk of T2DM or uncontrolled biochemical parameters. METHODS: We included 199 individuals with a T2DM diagnosis and 213 individuals without a T2DM diagnosis. Restriction fragment length polymorphism (RFLP) analyses were used to assess polymorphisms. RESULTS: We found a risk association between T2DM and uncontrolled biochemical parameters in a Mexican population for the genotypes del/del of NFκß, -174 and -572 of IL-6, C/C of IL-1ß, -308 and -238 of TNFα, and T/T of LPL. In subjects without diabetes (controls), we found an association between the G/C genotype of the -572 polymorphism and the G/C and C/C genotypes of the -597 polymorphism of IL-6 with the risk of glucose levels > 131 mg/dL. Genotype C/C of polymorphism -174 of the IL-6 gene was associated with high triglyceride levels, and levels > 5.8% of HbA1c were associated with the G/A genotype of TNFα -308. CONCLUSION: Here, we describe for the first time the relationship of T2DM risk and uncontrolled biochemical parameters with polymorphisms in the NFκß, IL-6, TNFα, IL-1ß, and LPL genes in a Mexican population. We also showed that for the population included in this study, there is an additive effect of the polymorphisms of the studied genes that considerably increases the risk of developing T2DM.We also showed that there are interactions between genes related to chronic inflammation that affect the risk of T2DM.

Pathological characteristics, survival, and risk of breast cancer associated with estrogen and xenobiotic metabolism polymorphisms in Mexican women with breast cancer.

Prolonged exposure to estrogens is the main factor associated with the risk and prognosis of breast cancer (BC). The genes involved in the biotransformation of estrogens and xenobiotics have allelic variants with modified enzymatic activities. We investigated the association of nine polymorphisms of some genes from the classical estrogen pathway with the risk of breast cancer and their role in the clinicopathological characteristics of poor clinical prognosis in a sample of Mexican women with BC. METHODS: We included 150 controls and 150 cases matched by age. To analyze the selected polymorphisms, TaqMan assays and high-resolution melting (HRM) analysis were used. RESULTS: The polymorphisms of the genes ERα, CYP1A1, CYP1B1, COMT, MGMT, and XRCC1 were positively associated with the BC risk. We found negative associations between CYP1B1G/G genotype and tumor size, and status of lymph node, estrogen receptor, triple negative, and survival. CONCLUSIONS: The polymorphisms included in this study are associated not only with the risk of BC, but also with some clinicopathological characteristics for poor prognosis of patients with breast cancer, highlighting the important role of CYP1B1 Leu432Val polymorphism.

COL1A1, CCDC170, and ESR1 single nucleotide polymorphisms associated with distal radius fracture in postmenopausal Mexican women.

Objective: The aim of this study was to analyze the genetic association of five ESR1 single nucleotide polymorphisms (SNPs) (rs3020331, rs851982, rs1999805, rs2234693, rs3020404), four COL1A1 SNPs (rs1800012, rs2075555, rs2412298, rs1107946), and two SNPs on the CCDC170 gene (rs9479055, rs4870044) with distal radius fracture (DRF) in a group of postmenopausal Mexican women.Methods: A case-control study was conducted. Cases (n = 182) were women above the age of 38 years with low-energy DRF, and controls (n = 201) were women without. Analysis was done through real-time polymerase chain reaction. Frequencies and Hardy-Weinberg equilibrium were calculated. A multivariate analysis including bone mass index, age, menarche, and menopause as covariables was carried out. Finally, haplotype and linkage disequilibrium (LD) analyses were performed.Results:COL1A1 rs1107946 was strongly associated with DRF. Both CCDC170 SNPs showed strong association with DRF. For the ESR1 gene, four SNPs (rs2234693, 3020404, rs3020331, and rs851982) showed very strong association with DRF. Additionally, the region between the latter two showed strong LD.Conclusions: A strong association of DRF with variants in these genes was found, including haplotypes and a region with strong LD on ESR1. The results suggest that these SNPs could be useful to detect the population at risk of presenting DRF among Mexican perimenopausal women.

Association of RMND1/CCDC170-ESR1 single nucleotide polymorphisms with hip fracture and osteoporosis in postmenopausal women.

OBJECTIVE: This study aimed to investigate the association of seven single nucleotide polymorphisms (SNPs) on the RMND1, CCDC170, and ESR1 genes with osteoporosis or hip fracture in a postmenopausal Mexican population. METHODS: We included a group of 400 postmenopausal women from the Health Workers Cohort Study from the Mexican Institute of Social Security. As a replication sample, we recruited 423 postmenopausal women from the National Institute of Rehabilitation. Demographic data were collected through a structured questionnaire. Bone mineral density was assessed using dual X-ray absorptiometry. Individuals were classified as normal, osteopenia, osteoporosis, and fracture, according to World Health Organization criteria. Genotyping was performed using predesigned TaqMan Probes. Linear regression analysis was used to investigate association. RESULTS: All of the analyzed SNPs showed association with at least one of the phenotypes of the study groups. In addition, we observed a region with linkage disequilibrium within the ESR1 gene in all groups. CONCLUSION: This study shows that an association of the SNPs can exist with osteopenia, osteoporosis, or fragility fracture. Our results agree with data published elsewhere, supporting the potential of these loci for the identification of the population at risk. However, additional studies are required to determine the extent of this association for other geographic regions of Mexico.

Molecular and clinical analysis in a series of patients with Pyknodysostosis reveals some uncommon phenotypic findings.

Pyknodysostosis is a rare autosomal recessive skeletal dysplasia characterized by short stature, deformity of the skull, osteosclerosis, hypoplasia of the clavicle, and bone fragility. Radiographs show increased bone density, osteosclerosis, and acroosteolysis of the terminal phalanges. The pycnodysostosis gene is located on chromosome 1q21 and encodes an enzyme called Cathepsin K. Cathepsin K is a cysteine protease lysosomal protein associated with the degradation of bone and cartilage. In the current study, the authors described the clinical, radiological and molecular features of a group of six Mexican patients, including two familial and two sporadic cases, with Pyknodysostosis. One of the patients presented hypoacusia, an unusual finding in this disease.

[Genetic diversity of 3 DNA probes in the DNA fingerprinting of a Mexican population]. / Diversidad genética de tres sondas de DNA en la huella digital de DNA de una población mexicana.

Each individual may be identified by characterizing its genetic material by DNA fingerprinting technology. Its application in Mexico demands a knowledge of the allelic and genotypic diversity of the DNA markers and the probability that two individuals may have the same fingerprint. In the present study the allelic and genotypic diversities of the loci D12S11 (MS43A), D7S22 (g3) and D1S7 (MS1) were determined in 100 Mexican students of the military school of medicine (Escuela Médico Militar de México). The mean allelic frequency of the loci MS43A, g3, and MS1 was 0.01, 0.008 and 0.006, respectively. The heterozygosity of MS43A and g3 was 98 and 99% for MS1. The probability that two individuals might have the same genetic pattern was 2.0 x 10(-4), 1.3 x 10(-4) and 7.2 x 10(-5) for the loci MS43A, g3 and MS1, respectively, and as low as 1.9 x 10(-12) for the three taken together. These data indicate that the genetic diversity of these DNA fingerprinting markers in the Mexican population is high enough to warrant its use in paternity testing and in the identification of individuals in forensic medicine.