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.

The association of single nucleotide polymorphisms in the calcitonin gene with primary osteoarthritis of the knee in Mexican mestizo population.

Primary osteoarthritis (OA) is a multifactorial disorder with several genetics factors involved. Calcitonin (CT) has been suggested to possess chondroprotective effects and could play an important role in the pathogenesis of OA. The aim of this study was to investigate whether genetic variations in or adjacent to the CT gene may be associated with primary OA of the knee in Mexican mestizo population. We conducted a case-control study to investigate the association between six single nucleotide polymorphisms at the CT locus and OA of the knee in 107 cases and 106 controls. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee ≥ 2. Controls were subjects >40 years of age with a radiologic score <2. Non-conditional logistic regression was developed to evaluate risk magnitude. The G allele and GT genotype frequencies of the G-706T polymorphism and the C allele and CC genotype of the C-778T polymorphism were significantly higher in patients with OA than in control subjects. The GG genotype of the G-706T was associated with lower risk of the development of OA of the knee. According to the results, the G-706T and the C-778T polymorphisms were related to the Cdx1 and Mzf1 transcription factor binding sites, respectively. Therefore, these could be related to regulation sequences in the CT gene promoter. In conclusion, G-706T and C-778T polymorphisms in the CT gene are significantly associated with the development of primary OA of the knee.

Association of the calcitonin gene (CA) polymorphism with osteoarthritis of the knee in a Mexican mestizo population.

Osteoarthritis (OA) is the most common form of destructive joint disease that is characterized by the degeneration of the articular cartilage, synovial membrane, joint capsule, and subchondral bone. The knee is a joint commonly affected for OA. Calcitonin (CT) has been suggested to have chondroprotective effects; therefore, could play a role in the pathogenesis of OA of the knee. Genetic variations in or adjacent to the CT gene may be associated with primary OA development. We conducted a case-control association study in which we examined the correlation between a dinucleotide (cytosine-adenine, CA) repeat polymorphism at the CT locus and OA of the knee in 88 patients with OA and in 111 control subjects from the Mexican mestizo population. Allele A and genotype AG frequencies were significantly higher in patients with OA than in control subjects (56.3 vs. 43.2%; p<0.001 and 40.9 vs. 26.1%; p=0.027, respectively), and were associated with the presence of OA of the knee (odds ratio [OR], 2.62; 95% confidence interval [95% CI], 1.30-5.27, and OR, 1.93; 95% CI, 1.04-3.58, respectively) using a logistic regression model adjusted for gender, age and Body mass index (BMI). The GG genotype was associated with a lower risk of OA development of the knee; thus, it may constitute a protective factor against this disease (OR, 0.40; 95% CI, 0.16-0.98). In summary, we conclude that the dinucleotide CA polymorphism in the CT gene may become a useful marker for genetic studies of OA of the knee in Mexican population.

Steroid sulfatase activity in leukocytes: a comparative study in 45,X; 46,Xi(Xq) and carriers of steroid sulfatase deficiency.

The enzyme steroid sulfatase (STS) hydrolyses 3-beta-hydroxysteroid sulfates. The female-male STS activity ratio is 1.04-1.7:1 in several cell lines in adults and reaches 2:1 in prepubertal subjects. In fibroblasts, STS values in X-chromosome abnormalities show a partial positive correlation according to the number of X-chromosomes. X-linked ichthyosis (XLI) carriers, with only one copy of the STS gene, present lower STS levels than normal controls. This study analyzes the STS activity in leukocytes of 46,Xi(Xq); 45,X; XLI carriers and normal controls using 7-[3H]-dehydroepiandrosterone sulfate as substrate. X-monosomy (1.07 +/- 0.18 pmol/mg protein/h), Xq isochromosome (1.02 +/- 0.12 pmol/mg protein/h) and normal females (1.03 +/- 0.11 pmol/mg protein/h) had similar STS values (p > 0.05). XLI-carriers and males showed the lowest STS levels (0.34 +/- 0.04 pmol/mg protein/h, p < 0.001 and 0.82 +/- 0.14 pmol/mg protein/h, p < 0.05, respectively). Female-male STS activity ratio in leukocytes was 1.3:1. These data indicate that a complex mechanism regulates the STS expression depending on each type of cell line.