Association of Polymorphisms in Estrogen Receptor Genes (ESR1 and ESR2) with Osteoporosis and Fracture-Involvement of Comorbidities and Epistasis.

Single-nucleotide polymorphisms (SNPs) in the ESR1/ESR2 genes play a role in osteoporosis (OP). Our objective was to determine associations of polymorphisms in ESR genes with OP and fracture, SNP-SNP interactions, and involvement of comorbidities. We analyzed 170 Mexican osteoporotic women (FNOP), 173 with hip fracture (HFx), and 210 controls. The SNPs, ESR1 rs2234693CC, rs851982CC and rs1999805AA, were associated with reduced OP risk (odds ratios [ORs] = 0.35, 0.40 and 0.32, respectively; p < 0.05); rs2234693CC was associated with reduced fracture risk (OR = 0.24; p < 0.05). The obese/overweight carriers of rs9340799GG had a lower OP (OR = 0.15, p = 0.016) and fracture (OR = 0.12, p = 0.0057) risk. The rs9479055AA and rs3020404AA hypertensive carriers had a higher OP risk (OR = 5.96, p = 0.032; and OR = 5.29, p = 0.02, respectively). In addition, rs3020404AA had a higher risk of fracture (OR = 4.90, p = 0.045). The rs2228480GG hypertensive carriers had a higher risk of fracture (OR = 6.22, p = 0.0038). We found a synergic relation between the ESR1 rs3020331 and rs1999805 in femoral neck OP and HFx. The rs2234693 (PvuII) and rs9340799 (XbaI) polymorphisms are associated with a high risk forming a haplotype. The epistasis analysis suggests the contribution of both genes (ESR1/ESR2) to the risk of OP and fracture. Epistasis and involvement of obesity and hypertension lead to a significant modification of the risk.

Estimation of absolute risk of fracture due to fragility in Mexican women with early and natural menopause.

BACKGROUND: Menopausal women lose until 5% of their bone density during the first years of menopause. One of 12 Mexican women will suffer a hip osteoporotic fracture after the age of 50. OBJECTIVE: To assess the absolute risk of major fracture (vertebrae, hip and forearm) and hip fracture and to establish the relation between years of menopause and bone mineral density (BMD). METHOD: A cross sectional analytical study, including women over 50 classified by early and natural menopause. Bone densitometry was performed and risk of fracture was calculated with FRAX (Fracture Risk Assessment Tool). RESULTS: From 209 women, 32% had early menopause and 68% had natural menopause. The average age were 67.4 ± 9.2 vs. 65.9 ± 8.3 years; they had 27.3 ± 9.4 vs. 15.2 ± 8.4 years of menopause (p ≤ 0.01); the hip BMD was 0.6286 ± 0.115 vs. 0.6789 ± 0.132 g/cm2 (p ≤ 0.05), with a T-score of -2.11 ± 0.979 vs -1.70 ± 1.129 (p ≤ 0.05), respectively. The 10 years risk probability for major fractures was 8.8 ± 4.7 vs. 7.4 ± 4.7 (p ≤ 0.05) and for hip fractures was 3.2 ± 3.0 vs. 2.5 ± 2.9 (p > 0.05). CONCLUSIONS: We recommend to take into account the clinical importance of the years of menopause and the type of menopause, as factors that influence the bone density decrease and the increase of future fractures risk.

ANTECEDENTES: La mujer pierde hasta un 5% de densidad ósea durante los primeros años de menopausia. En México, una de cada 12 mujeres tendrá una fractura de cadera por fragilidad después de los 50 años. OBJETIVO: Estimar el riesgo absoluto de fractura mayor (vertebrales, cadera y antebrazo) y de fractura de cadera, y establecer la relación entre los años de menopausia y la densidad mineral ósea (DMO). MÉTODO: Diseño transversal, analítico y comparativo. Se incluyeron mujeres mayores de 50 años, agrupadas en menopausia temprana y natural. Se realizó densitometría ósea y se calculó el riesgo de fractura con el FRAX (Fracture Risk Assessment Tool). RESULTADOS: Se estudiaron 209 mujeres, el 32% con menopausia temprana y el 68% con menopausia natural, de una edad promedio de 67.4 ± 9.2 y 65.9 ± 8.3 años, respectivamente, con 27.3 ± 9.4 y 15.2 ± 8.4 años (p ≤ 0.01) con menopausia. La DMO de cadera fue de 0.6286 ± 0.115 y 0.6789 ± 0.132 g/cm2 (p ≤ 0.05), y la T-score fue de −2.11 ± 0.979 y −1.70 ± 1.129, respectivamente (p ≤ 0.05). Las probabilidades de riesgo a 10 años para fracturas mayores fueron de 8.8 ± 4.7 y 7.4 ± 4.7 (p ≤ 0.05), y para fractura de cadera fueron de 3.2 ± 3.0 y 2.5 ± 2.9 (p > 0.05), respectivamente. CONCLUSIONES: Se recomienda considerar la importancia clínica de los años de menopausia y del tipo de menopausia como factores que influyen en la disminución de la DMO y elevan el riesgo para futuras fracturas.

Association of the IL6 rs1800796, but not of the IL6 rs1800795, IL6R rs4845617 and rs2228145 polymorphisms with hip fracture in elderly Mexican women.

BACKGROUND AND AIMS: Polymorphisms in Interleukin-6 (IL6) and its receptor (IL6R) have been associated with bone mineral density. In this work, the G-174C and G-572C polymorphisms in IL6, G-208A, and Asp358Ala in IL6R were analyzed in Mexican women with hip fracture. METHODS: Postmenopausal Mexican women (60 years or over) with hip fragility fracture (77.97 ± 8 years) and without hip fracture (70.5 ± 7.02 years) were genotyped by real-time PCR. RESULTS: The rs1800796 GG genotype was associated with low risk of fracture (p = 0.05), while GC genotype was associated with high risk of fracture [p = 0.047, OR 2.3 (95% CI 1.013-5.2)]. The AA genotype of the rs2228145 SNP (IL6R) was significantly different [p = 0.033, OR 1.94 (95% CI 1.01-3.75)], but when data were adjusted by age and body mass index, there were no differences (p = 0.9). CONCLUSION: Our results suggest that the IL6 rs1800796 SNP is a good marker for hip fracture risk in Mexican women.

Association of the COL1A1 gene polymorphisms in Mexican postmenopausal women with fracture or with low bone mineral density at the hip.

BACKGROUND AND AIMS: Osteoporosis leads to high fracture risk and evidence suggests that genetic factors play an important role in this disease. The aim was to evaluate the association of two polymorphisms (-1997G/T, +1245G/T) in the collagen type1 alpha 1 gene (COL1A1) with fracture or with low bone mineral density (BMD) at the hip in postmenopausal Mexican women. METHODS: BMD was determined by bone densitometry and the risk factors were collected with a questionnaire. Genotyping was performed by real-time PCR. RESULTS: The polymorphisms were in Hardy-Weinberg equilibrium. The -1997G/+1245T haplotype showed, after adjustment for confounders, a fourfold increased risk of hip fracture [OR 4.32; p = 0.041 (95 % CI 1.07-17.43)]; while in the women with low BMD at the hip, the risk was increased threefold [OR 3.36; p = 0.022 (95 % CI 1.20-9.40)]. CONCLUSIONS: The results support the association of COL1A1 gene polymorphisms with fracture and with low BMD at the hip in Mexican population.

Effect of Helicobacter pylori infection on gastric ghrelin expression and body weight.

BACKGROUND & AIM: Ghrelin is a peptide mainly produced by gastric tissue playing an important role in energy homeostasis. It has been suggested that inflammatory and atrophic events induced by Helicobacter pylori (H. pylori) infection in gastric mucosa compromise the survival of the ghrelin-producing cells. The aim of this study was to investigate the effect of H. pylori infection on gastric ghrelin expression and body weight. METHODS: Consecutive patients referred for upper endoscopy were invited to participate. Patients with H. pylori infection (determined by histology) were defined as cases and patients without infection as controls. The density of colonization was classified in mild, moderate, or severe infection. Body mass index (BMI) was calculated. Ghrelin-immunoreactive cells were quantified in gastric biopsies by immunohistochemical staining. RESULTS: We studied 189 cases (92 males, 97 females) and 94 controls (55 males, 39 females). Cases were older (48.16 +/- 16.44 vs. 42.88 +/- 17.04 years, p < 0.05) and exhibited a lower percentage of ghrelin-immunoreactive cells (2.13% vs. 10.43%, p < 0.05) than controls. The prevalence of obesity was significantly lower than normal-weight among all cases, independently of the severity of infection (mild infection, 17.6% vs. 47.3%, p = 0.001; moderate-severe infection, 10.4% vs. 50%, p = 0.001). Univariate analysis showed a non-significant trend suggesting a protective effect of H. pylori against obesity. Nevertheless, BMI did not differ significantly between cases and controls. CONCLUSION: Chronic H. pylori infection contributes to a lower percentage of gastric ghrelin-immunoreactive cells but has no effect on the body weight of infected patients.

Low serum levels of ghrelin are associated with gallstone disease.

AIM: To explore the role of ghrelin in gallstone disease. METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI), serum insulin, ghrelin, and serum lipids were measured. Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations. RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA. CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.

Carcinoma anaplásico de tiroides en el Instituto Nacional de la Nutrición Salvador Zubirán / Anaplastic carcinoma of the Thyroid at the Instituto Nacional de la Nutricion Salvador Zubiran

Antecedentes. El carcinoma anaplástico de tiroides (CAT) es un tumor muy agresivo cuya supervivencia media después del diagnóstico es de seis meses. Su rareza ha limitado el conocimiento de muchas de sus características clínicas y de evolución. Objetivo. Analizar la forma de presentación, diagnóstico, tratamiento y superviviencia de los pacientes con CAT, así como sus características morfológicas, inmunohistoquímicas y contenido nuclear de DNA. Pacientes y métodos. Fueron 12 pacientes con CAT (11 mujeres) con edad promedio de 65 años y que recibieron atención en nuestra institución de 1970 a 1995. La información clínica se obtuvo de los expedientes y para los análisis morfológico, inmunohistoquímico y genético se emplearon laminillas provenientes de bloques de tejido archivado. Resultados. En 10 pacientes se documentó coexistencia de enfermedad tiroidea (9 bocios y un Graves). La presentación más frecuente fue una tumoración de crecimiento rápido acompañada de disfagia, dolor cervical, disfonía y disnea que en 10 correspondió gamagráficamente a un nódulo frío. En todos se corroboró el diagnóstico por biopsia o por histología. El patrón celular predominante fue fusiforme. Se encontró coexistencia con carcinoma papilar en ocho pacientes. En seis casos estudiados, se demostró positividad para S-100 y vimentina en todos, en 5 (83 por ciento) se detectó el antígeno de membrana epitelial, el antígeno carcinoembrionario en la mitad, para tiroglobulina y calcitonina en 2/6 casos, y para enolasa neuronal específica en 1/6. La citometría de flujo mostró un patrón diploide de DNA en los 6 casos evaluados. Se logró resección completa en 2/11 sometidos a cirugía. Conclusiones. El CAT es un tumor agresivo que se asocia con otras enfermedades tiroideas. El patrón morfológico predominante es el fusiforme, con frecuente reactividad para vimentina, S-100 y antígeno de membrana epitelial, y un patrón diploide de DNA

Macrofollicular Variant of Papillary Thyroid Carcinoma: A Case and Control Analysis.

The planimetric, flow cytometric, and immunohistochemical characteristics of the macrofollicular variant of papillary thyroid carcinoma (MFVPTC) have not been reported before. The clinical, morphological, immunohistochemical, planimetric, and flow cytometric characteristics of six cases of the MFVPTC and six of the follicular variant of papillary thyroid carcinoma (FVPTC) were analyzed. Patients had undergone surgical treatment. The mean age was 38 (range 29-64 yr), and five were women. Tumors had a mean size of 3.2 cm (range 0.3-4.5 cm). Half were originally diagnosed as goiter. Macrofollicles had a mean diameter of 345.5 um, perimeter of 1237 um, and area of 13,779 um(2), with nuclear changes of PTC. Mean follow-up was 107 mo (range 12-277), and neither lymph node metastases nor recurrence were seen. Differences in diameter, perimeter, and area between the macrofollicular and follicular variants were found. Follicular neoplastic cells were thyroglobulin and 5-100 protein positive in macrofollicles and normofollicles. All were negative to cytokeratin and to high-mol-wt keratin. All tumors were diploid. There were no significant differences in follow-up, DNA content, nor immunohistochemical reactivity. Differences in diameter (p < 0.00006), perimeter (p < 0.0001), and area (p < 0.001) were observed. It is important to recognize this variant because it could be misdiagnosed as benign thyroidal lesions.