Long Non-coding RNA LINC-PINT and LINC00599 Polymorphisms are Associated With High-altitude Pulmonary Edema in Chinese

BackgroundHigh-altitude pulmonary edema (HAPE) is a kind of non-cardiogenic edema with high incidence and life-threatening. This study was designed to explore the association of LINC-PINT and LINC00599 polymorphisms with HAPE susceptibility.MethodsThis study included 244 HAPE patients and 243 age-, sex-matched healthy controls from the Chinese population. The genotypes of polymorphisms were detected using the Agena MassARRAY. The relationship between polymorphisms and HAPE risk was evaluated using a χ² test with an odds ratio (OR) and 95% confidence intervals (CIs) in multiple genetic models.ResultsWe observe a significant association between the rs157928 and decreased HAPE risk in genotype model (OR = 0.65, 95% CI = 0.43–0.98, p = 0.038). The subgroup analysis results indicated that rs2272026 was associated with a decreased risk of HAPE in younger patients with age ≤32 (codominant model: p = 0.006; recessive model: p = 0.005 additive model: p = 0.018; and allele model: p = 0.012; rs72625676, codominant model: p = 0.038; recessive model: p = 0.037). Among patients older than 32 years, there was a significantly increased risk of HAPE associated with the rs2272026 and rs1962430 (rs2272026: genotype model: p = 0.049; recessive model: p = 0.029; rs1962430: genotype model: p = 0.024; recessive model: p = 0.020). Nevertheless, rs157928 had relationship with significantly reducing the risk of HAPE in the genotype model (p = 0.018).ConclusionOur study suggests that LINC-PINT and LINC00599 polymorphisms are associated with HAPE susceptibility in Chinese population.     

Association of vitamin D receptor gene TaqI,BsmI, FokI and ApaI polymorphisms and susceptibility to extremity chronic osteomyelitis in Chinese population

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of several inflammatory diseases. However, potential association of the VDR gene polymorphisms with susceptibility to extremity chronic osteomyelitis remains unclear. The present study aimed to investigate link between VDR gene polymorphisms and the risk of extremity chronic osteomyelitis in Chinese population. A total of 233 patients with chronic osteomyelitis and 200 healthy controls were genotyped for the 4 single-nucleotide polymorphisms (SNPs) (TaqI, BsmI, FokI and ApaI) in VDR gene using the SNaPshot genotyping method. The frequencies of mutant allele C in rs731236 (P = 0.044, OR = 1.830, 95% CI 1.009 − 3.319) and rs2228570 (P = 0.029, OR = 1.347, 95% CI 1.031 − 1.761) were significantly higher in patients than those in healthy controls. In addition, outcomes of the logistic regression analysis adjusted by gender and age revealed that significant links were found between rs731236 (P = 0.05, OR = 1.887, 95% CI 1.001 − 3.558), rs2228570 (P = 0.042, OR = 1.594, 95% CI 1.016–2.500) and the risk of developing chronic osteomyelitis by dominant genetic model. In addition, significant association was also found between rs2228570 and the risk of developing the disease by homozygous model (P = 0.034, OR = 1.803, 95% CI 1.046 − 3.106). However, no significant correlations were found between BsmI (rs1544410) or ApaI (rs7975232) gene polymorphisms and the susceptibility to the disease. To our knowledge, we reported for the first time that VDR gene TaqI (rs731236) and FokI (rs2228570) polymorphisms may contribute to the increased risk of chronic osteomyelitis in Chinese population.     

Association of IL-2RA and IL-2RB genes with erosive status in early rheumatoid arthritis patients (ESPOIR and RMP cohorts)

ObjectivesTo assess the impact of single nucleotide polymorphisms (SNPs) in IL-2RA (rs2104286) and IL-2RB (rs743777 and rs3218253) genes on the risk of erosions in rheumatoid arthritis (RA) patients.MethodsThis work is derived from 2 prospective cohorts of early RA: ESPOIR (n = 439) and RMP (n = 180). The proportions of patients with erosions at baseline and 1 year according to the genotypes of IL2RA (rs2104286) or the haplotypes constructed with the 2 SNPs of IL2RB were compared in the whole population and in ACPA positive patients. A meta-analysis assessing the risk of erosion depending on the haplotypes of the 2 SNPs of IL-2RB was performed using the Mantel-Haenszel method. A multivariate model was used to assess the independent effect of the haplotypes of IL-2RB on the risk of erosions.ResultsThe AC haplotype of IL-2RB carriage was significantly associated with the rate of erosions in ACPA positive patients in ESPOIR cohort (rate of erosions: AC/AC: 78% versus GC or GT/GC or GT: 44%, p = 0.001). A meta-analysis of ESPOIR and RMP cohorts confirmed that the carriage of AC haplotype was significantly associated with the rate of erosions at 1 year in the whole sample (OR[95%CI] = 1.92[1.14–3.22], p = 0.01) and in ACPA positive patients (OR[95%CI] = 3.34[1.68–6.67], p = 0.0006). A multivariate model in ESPOIR cohort demonstrated the independent effect of the carriage of the AC haplotype (6.03[1.94–18.69], p = 0.002) on the risk of erosions in ACPA+ patients.ConclusionA haplotype constructed with 2 SNPs located on IL-2RB gene was associated with erosive status in early RA.     

Mannose-binding lectin-2 and ficolin-2 gene polymorphisms and clinical risk factors for acute rejection in kidney transplantation

IntroductionThere is growing evidence that the lectin pathway is significantly associated with acute rejection. Rare studies associated both gene polymorphisms of MBL2 and FCN2 with acute rejection after kidney transplantation. The aim of the present study was to investigate the role of the lectin gene profile and clinical risk factors such as PRA level on acute rejection in kidney transplant recipients.MethodsWe prospectively analyzed 157 kidney transplant recipients with and without acute rejection. A total of 6 well-known functional single-nucleotide polymorphisms in the MBL2 gene and 5 in the FCN2 gene of the recipients were determined by gene sequencing. MBL2 and FCN2 genotypic variants were analyzed for association with the incidence of acute rejection within the first year after kidney transplantation.ResultsAfter adjusting for variables of P < 0.2, we found the differences in the incidence of acute rejection were only according to panel-reactive antibodies (odds ratios (OR) = 6.468, 95% confidence intervals (CI) = 2.017–20.740, P = 0.002) and the HH genotypes of MBL2 promoter ? 550 (OR = 2.448, 95%CI = 1.026–5.839, P = 0.044).ConclusionPanel-reactive antibodies and the HH genotypes of MBL2 promoter ? 550 have significant impacts on the risk of developing acute rejection after kidney transplantation.     

HLA-DRB1 Alleles are Associated With COPD in a Latin American Admixed Population

IntroductionWhile the molecular mechanisms of COPD pathogenesis remain obscure, there is mounting evidence supporting a key role for autoimmunity. Although human leukocyte antigens (HLA) alleles have been repeatedly associated with autoimmune processes, the relation between HLA and COPD remains largely unexplored, especially in Latin American (LA) populations. Consequently, this study aimed to investigate the presence of HLA class I and II alleles in COPD patients and healthy controls in a LA population with admixed ancestry.MethodsCOPD patients (n = 214) and age-matched controls (n = 193) were genotyped using the Illumina Infinium Global Screening Array. The classic HLA alleles were imputed using HLA Genotype Imputation with Attribute Bagging (HIBAG) and the Hispanic reference panel. Finally, the distribution of HLA-DRB1 alleles was reexamined in 510 randomly recruited unrelated volunteers.ResultsCODP patients showed a higher HLA-DRB1*01:02 allele frequency (6.54%) than healthy controls (3.27%, p = 0.04, OR = 2.07). HLA-DRB1*01:02 was also significantly associated with FEV₁ (p = 0.04) and oxygen saturation (p = 0.02), and the FEV₁/FVC ratio was higher in HLA-DRB1*15:01-positive patients (p = 9 × 10^?3).ConclusionWe report an association among HLA-DRB1 alleles, COPD risk and pulmonary function parameters for the first time in Latin Americans. Since HLA-DRB1 genetic variability relates to the individual autoimmune response, these results support a role of autoimmunity in the pathogenesis of COPD.     

Oncological outcomes of laparoscopic nephroureterectomy with pluck method for distal ureter resection

ObjectiveTo report the oncologic outcomes of upper tract urothelial carcinoma treated with laparoscopic nephroureterectomy and pluck method for distal ureter resection.Materials and methodsBetween May 2004 and November 2015, 118 patients with upper urinary tract urothelial carcinoma received laparoscopic radical nephroureterectomy with endoscopic bladder cuff excision at our institution. The medical records were reviewed retrospectively for clinical and pathological results. Cox regression analyses were performed on factors related to oncological outcomes.ResultsThe median follow-up was 26 months. Bladder recurrence was found in 27 patients (22.9%), extravesical retroperitoneal recurrence in four patients (3.4%), and metastases in 17 patients (14.4%). Multivariate analyses showed that male sex was associated with higher bladder recurrence [odds ratio (OR) = 2.2; 95% confidence interval (CI), 1.02–4.78; p = 0.045)], tumor size had significant correlation with locoregional recurrence (OR = 1.29; 95% CI, 1.07–3.43; p = 0.029), tumor stage was significantly correlated with subsequent metastasis (OR = 2.08; 95% CI, 1.21–3.56; p = 0.008) and overall survival (OR = 1.84; 95% CI, 1.06–3.22 ; p = 0.031), and tumor size correlated significantly with cancer-specific survival (OR = 2.57; 95% CI, 1.16–5.72; p = 0.021).ConclusionsTumor size and tumor stage were significantly associated with survival (cancer-specific and overall survival) in patients receiving nephroureterectomy with pluck method.     

Psoas Muscle Density Evaluated by Chest CT and Long-Term Mortality in COPD Patients

RationalePoor muscle quality in COPD patients relates to exercise intolerance and mortality. Muscle quality can be estimated on computed tomography (CT) by estimating psoas density (PsD). We tested the hypothesis that PsD is lower in COPD patients than in controls and relates to all-cause mortality.MethodsAt baseline, PsD was measured using axial low-dose chest CT images in 220 COPD patients, 80% men, who were 65 ± 8 years old with mild to severe airflow limitation and in a control group of 58 subjects matched by age, sex, body mass index (BMI) and body surface area (BSA). COPD patients were prospectively followed for 76.5 (48–119) months. Anthropometrics, smoking history, BMI, dyspnoea, lung function, exercise capacity, BODE index and exacerbations history were recorded. Cox proportional risk analysis determined the factors more strongly associated with long-term mortality.ResultsPsD was lower in COPD patients than in controls (40.5 vs 42.5, p = 0.045). During the follow-up, 54 (24.5%) deaths occurred in the COPD group. PsD as well as age, sex, pack-year history, FEV₁%, 6MWD, mMRC, BODE index, were independently associated with mortality. Multivariate analysis showed that age (HR 1.06; 95% CI 1.02–1.12, p = 0.006) and CT-assessed PsD (HR 0.97; 95%CI 0.94–0.99, p = 0.023) were the variables independently associated with all-cause mortality.ConclusionsIn COPD patients with mild to severe airflow limitation, chest CT-assessed psoas muscle density was lower than in matched controls and independently associated with long-term mortality. Muscle quality using the easy to evaluate psoas muscle density from chest CT may provide clinicians with important prognostic information in COPD.     

Collagen gene polymorphisms influence fracture risk and bone mass acquisition during childhood and adolescent growth

Fractures are common in childhood with incidence maximal during puberty, around the time of peak height velocity. The relationships between single nucleotide polymorphisms (SNPs) in COL1A1 and COL1A2, bone mass acquisition, and childhood fractures are unclear.We recruited 394 children and adolescents aged 4 to 16 years into a noninterventional case control study. All had suffered an episode of trauma leading to hospital presentation; 205 had sustained a fracture. We determined the frequency of COL1A1 Sp1 and COL1A2 PvuII SNPs. Lumbar spine dual-energy X-ray absorptiometry (DXA) measurements were compared between fracture and control groups according to genotype. Subgroup analyses were performed according to sex, pubertal status, and site of injury.We found that the COL1A2 ‘PP’ genotype approximately halved the odds of fracture in the study group as a whole (OR = 0.45 [95% CI = 0.24–0.82], p = 0.01). In particular, possession of the same genotype by subjects who had not yet progressed beyond midpuberty was associated with reduced odds of fracture (OR = 0.38 [95% CI = 0.19–0.79], p = 0.01) and significantly increased lumbar spine bone mineral content (p = 0.03) and areal bone mineral density (p = 0.007). The COL1A1 Sp1 binding site ‘s’ allele was associated with a trebling of the odds of fracture in prepubertal children (OR = 3.1 [95% CI = 1.43–6.61], p = 0.004), but there was no association with any DXA measures.This is the first paediatric study to our knowledge that shows an association of the COL1A2 PvuII restriction site ‘PP’ genotype with a reduced risk of fracture and of the COL1A1 Sp1 binding site ‘s’ allele with an increased risk. The association of these variants with fracture risk is greatest during periods of predominantly appendicular bone growth.     

Vertebral fracture risk factors in postmenopausal women over 50 in Valencia,Spain. A population-based cross-sectional study

PurposeThis study aims to estimate the prevalence of risk factors for osteoporotic vertebral fracture and analyze the possible associations between these factors and the presence of densitometric osteoporosis and prevalent morphometric vertebral fracture.MethodsData from a population-based cross-sectional sample of 804 postmenopausal women over the age of 50 years old living in the city of Valencia (Spain) were used. The women were interviewed to identify the prevalence of osteoporotic fracture risk factors and underwent a densitometry and a dorsolumbar spine X-ray.ResultsThe most prevalent risk factors were densitometric osteoporosis (31.7%), history of parental hip fracture (19.4%), hypoestrogenism (19%), and body mass index (BMI) ≥ 30 kg/m² (35.2%). After adjusting for all covariables, densitometric osteoporosis was associated with increased age [odds ratio (OR)_{65–69 years}: 2.84, 95% confidence interval (CI): 1.75–4.61; OR_{70–74 years}: 4.01, 95% CI: 2.47–6.52; OR_75 + years: 5.96, 95% CI: 3.27–10.87] and inversely associated with high BMI (OR_25.0–29.9: 0.51, 95% CI: 0.34–0.76; OR_≥ 30: 0.30, 95% CI: 0.19–0.46). Morphometric vertebral fracture was associated with age (OR_{65–69 years}: 2.04, 95% CI: 1.03–4.05; OR_{70–74 years}: 4.05, 95% CI: 2.11–7.77; OR_75 + years: 8.43, 95% CI: 3.97–17.93), poor educational level (OR: 1.70, 95% CI: 1.06–2.72) and with densitometric osteoporosis and BMI ≥ 30 kg/m² (OR: 3.35, 95% CI: 1.85–6.07).ConclusionsThe most prevalent osteoporotic fracture risk factors were having a high BMI and the presence of densitometric osteoporosis. A higher risk of morphometric vertebral fracture in women with both low bone mineral density and high BMI was found. This association, if confirmed, has important implications for clinical practice and fracture risk tools. We also found a higher risk in women with a poor educational level. More attention should be addressed to these populations in order to control modifiable risk factors.     

Association between the CX3CR1 gene V249I polymorphism and delayed kidney allograft function

BackgroundFractalkine is a member of the chemokine family that acts as an adhesion molecule and as an extracellular chemoattractant promoting cellular migration. In this study, we analysed the association between the CX3CR1 gene V249I (rs3732379) SNP and renal allograft function.MethodsThe study enrolled 270 Caucasian kidney allograft recipients. The following parameters were recorded in each case: the recipient's age and gender, delayed graft function (DGF) defined as the need for dialysis in the first 7 days after transplantation, occurrence and number of episodes of acute rejection (AR), and chronic allograft dysfunction (CAD).ResultsDelayed graft function was diagnosed in 39.2% of individuals with the CC genotype, 22.7% with CT and 23.5% of those with the TT genotype. The differences were statistically significant (CC vs. TT + CT: OR = 2.17; 95% CI = 1.28–3.70, p = 0.0042). In multivariate analysis the CC genotype was an independent and significant predictor of higher risk of DGF. The distribution of genotypes and alleles of the CX3CR1 gene polymorphism among patients with and without AR as well as CAD did not differ significantly.ConclusionsThe results of this study suggest that the CX3CR1 gene V249I (rs3732379) SNP CC genotype is associated with increased risk of DGF.     

Polymorphisms in the estrogen receptor genes are associated with hip fractures in Chinese

IntroductionHip fractures (HF) are a major cause of public health burden with strong genetic determination. However, the true causal genes remain largely unknown.Materials and methodsBased on the important biological role of estrogens in bone homeostasis, this study aimed to investigate whether the estrogen receptor genes, ESR1 and ESR2, affect the onset of HF in 700 elderly Chinese subjects (350 with osteoporotic HF and 350 healthy controls). We genotyped 32 SNPs in total and examined their associations both by the single-SNP and haplotype tests.ResultsWe identified two novel SNPs of ESR1, rs3020314 and rs1884051, were significantly associated with HF (rs3020314: P = 0.0004, OR = 1.66, 95%CI: 1.25–2.18; rs1884051: P = 0.0004, OR = 1.46, 95%CI: 1.19–1.81). We firstly detected significant association of ESR2 with HF (rs960070: P = 0.0070, OR = 1.43, 95%CI: 1.10–1.86). Haplotype analyses corroborated our single-SNP results.ConclusionOur findings have important implications for understanding the pathology of osteoporotic fractures. Independent replication studies are needed to validate our results and explore the most possible functional variants for molecular studies.     

Prevalence and Determinants of COPD in Spain: EPISCAN II

BackgroundTwo previous national epidemiological studies, IBERPOC in 1997 and EPISCAN in 2007, determined the COPD burden in Spain. Changes in demographics and exposure to risk factors demand the periodic update of COPD prevalence and its determinants.MethodsEPISCAN II aimed to estimate the prevalence of COPD in the general population aged 40 years or older in all 17 regions of Spain. A random population screening sample, requiring 600 participants per region performed a questionnaire plus post-bronchodilator (post-BD) spirometry.ResultsA total of 12,825 subjects were initially contacted, and 9433 (73.6%) agreed to participate, of whom 9092 performed a valid spirometry. Baseline characteristics were: 52.6% women, mean ± SD age 60 ± 11 years, 19.8% current- and 34.2% former-smokers. The prevalence of COPD measured by post-BD fixed ratio FEV₁/FVC < 0.7 was 11.8% (95% C.I. 11.2–12.5) with a high variability by region (2.4-fold). Prevalence was 14.6% (95% C.I. 13.5–15.7) in males and 9.4% (95% C.I. 8.6–10.2) in females; according to the lower limit of normal (LLN) was 6.0% (95% C.I. 5.5–6.5) overall, by sex being 7.1% (95% C.I. 6.4–8.0) in males and 4.9% (95% C.I. 4.3–5.6) in females. Underdiagnosis of COPD was 74.7%. Cases with COPD were a mean of seven years older, more frequently male, of lower attained education, and with more smokers than the non-COPD population (p < 0.001). However, the number of cigarettes and pack-years in non-COPD participants was substantial, as it was the reported use of e-cigarettes (7.0% vs. 5.5%) (p = 0.045). There were also significant social and clinical differences including living alone, previous respiratory diagnoses, more comorbidities measured with the Charlson index, greater BODE and COTE scores, cognitive impairment, and depression (all p < 0.001).ConclusionsCOPD remains prevalent in Spain and frequently underdiagnosed.     

Candidates to salvage therapy after external-beam radiotherapy of prostate cancer: Predictors of local recurrence volume and metastasis-free survival

PurposeThe purpose of this study was to assess the predictors of metastasis-free survival (MFS) and of the volume of the local recurrence in patients with rising prostate-specific antigen (PSA) serum level after radiotherapy for prostate cancer and referred for prostate magnetic resonance imaging (MRI) and biopsy in view of salvage treatment.Materials and methodsA total of 132 consecutive men (median age, 70 years; IQR, 66–77 years) with rising PSA after prostate radiotherapy who underwent prostate MRI and biopsy in view of salvage treatment between January 2010 and July 2017 were retrospectively evaluated at a single center. MFS predictors were assessed with Cox models. Predictors of the volume of the local recurrence (number of invaded prostate sectors at biopsy) were assessed using Poisson regression among variables available at PSA relapse.ResultsAt multivariate analysis, an initial Gleason score ≥ 8 (OR = 7 [95% confidence interval (CI): 1.2–40]; P = 0.03), a recent radiotherapy (OR = 17 [95% CI: 3.9–72]; P < 0.0001), the use of androgen deprivation therapy at PSA relapse (OR = 12.5 [95% CI: 2.8–57]; P = 0.001) and the number of invaded prostate sectors (OR = 1.5 [95% CI: 1.1–2]; P = 0.007) and maximum cancer core length (OR = 0.7 [95%CI: 0.6–0.9]; P = 0.002) at biopsy performed at PSA relapse were significant MFS predictors. The PSA level at relapse was significant independent predictor of the volume of local recurrence only when used as a continuous variable (P = 0.0002) but not when dichotomized using the nadir + 2 threshold (P = 0.41).ConclusionPathological and clinical factors can help predict MFS in patients with rising PSA after prostate radiotherapy and candidates to salvage treatment. The PSA level at relapse has strong influence on the local recurrence volume when used as a continuous variable.     

Comprehensive assessment of sensitizing events and anti-HLA antibody development in women awaiting kidney transplantation

BackgroundAlloimmunization remains a critical factor which affects the success of kidney transplantation. Patients awaiting solid organ transplantation may develop anti-HLA antibodies after pregnancies, transfusions and previous events of transplantations.AimWe evaluated the effects of different sensitizing events on the anti-HLA antibody production and the potential role of patient HLA alleles in the context of antibody development in both the overall and pregnancy sensitized groups.Material and methodsWe retrospectively stratified 411 women on waiting list for kidney transplantation by route of sensitization. The presence of anti-HLA antibodies was evaluated by Solid Phase Assay and HLA typing was performed by serological and molecular methods.ResultsIn our study population, 54% of women had anti-HLA antibodies. We found that the 51.6% of women with pregnancy only, 44% of women with transfusion only and 100% of women with a history of transplantation only developed anti-HLA antibodies. Pregnancy only resulted significantly associated with all anti-HLA antibody development such as anti-A, -B, -C, -DR, -DP as well as anti-DQB and -DQA antibodies. We investigated the influence of patient HLA alleles on the antibody development in the overall study population. Patients expressing HLA A*32 (p = 0.024, OR = 0.42), B*14 (p = 0.035, OR = 0.44), HLA-B*44 (p = 0.026, OR = 0.51) and DRB1*01 (p = 0.029, OR = 0.55) alleles produced anti-HLA antibodies less frequently compared to subjects with other alleles. In the pregnancy only group, B*14 (p = 0.010, OR = 0.12) and B*51 (p = 0.005, OR = 0.24) alleles were associated with a low risk of anti-HLA antibody development, while A*11 (p = 0.033, OR = 3.56) and DRB1*04 (p = 0.022, OR = 3.03) alleles seem to represent a higher risk.ConclusionsPregnancy still remains a strong sensitizing event in women awaiting kidney transplantation. The anti-HLA antibody development in pregnancy appears to be associated with the expression of particular HLA alleles.     

Association between common risk factors and molecular subtypes in breast cancer patients

BackgroundBreast cancer is the most commonly diagnosed cancer in women worldwide and characterized its by molecular and clinical heterogeneity. Gene expression profiling studies have classified breast cancers into five subtypes: luminal A, luminal B, HER-2 overexpressing, basal-like, and normal breast-like. Although clinical differences between subtypes have been well described in the literature, etiologic heterogeneity have not been fully studied. The aim of this study was to assess the associations between several hormonal and nonhormonal risk factors and molecular subtypes of breast cancer.MethodsThis cross-sectional study consisted of 1884 invasive breast cancer cases. Variables studied included family history, age at first full-term pregnancy, number of children, duration of lactation, menstruation history, menopausal status, blood type, smoking, obesity, oral contraceptive use, hormone replacement therapy and in vitro fertilization. The odds ratios (OR) and 95% confidence intervals (CI) were estimated using multivariate logistic regression analysis.ResultsThousand two-hundred and forty nine patients had luminal A, 234 had luminal B, 169 had HER-2 overexpressing and 232 had triple negative breast cancer. The age of ≥40 years was found to be a risk factor for luminal A (OR 1.41 95% CI 1.15–1.74; p = 0.001) and HER-2 overexpressing subtype (OR: 1.51, 95% CI: 1.01–2.25; p = 0.04). Women who were nulliparous (OR 1.48, 95% CI 1.03–2.13; p = 0.03) or who had their first full-term pregnancy at age 30 years or older (OR 1.25 95% CI 0.83–1.88; p = 0.04) were at increased risk of luminal breast cancer, whereas women with more than two children had a decreased risk (OR 0.68, 95% CI 0.47–0.97; p = 0.03). Breast-feeding was also a protective factor for luminal subtype (OR 0.74, 95% CI 0.53–1.04; p = 0.04) when compared to non-luminal breast cancer. We found increased risks for postmenopausal women with HER-2 overexpressing (OR 2.20, 95% CI 0.93–5.17; p = 0.04) and luminal A (OR 1.87, 95% CI 0.93–3.90, p = 0.02) breast cancers, who used hormone replacement therapy for 5 years or more. Overweight and obesity significantly increased the risk of triple negative subtype (OR 1.89 95% CI 1.06–3.37; p = 0.04 and OR 1.90 95% CI 1.00–3.61; p = 0.03), on the contrary, decreased the risk of luminal breast cancer (OR 0.63 95% CI 0.43–0.95; p = 0.02 and OR 0.50 95% CI 0.32–0.76; p = 0.002, respectively) in premenopausal women. There were no significant differences between risk of breast cancer subtypes and early menarche, late menopause, family history, postmenopausal obesity, oral contraseptive use, smoking, in vitro fertilization, blood groups and use of hands.ConclusionsReproductive and hormonal characteristics (breastfeeding, parity, age at first full-term birth, hormone replacement therapy) were associated with luminal subtype, compared to non-luminal breast cancer, as consistent with previous studies. Obesity and overweight increased the risk of triple negative subtype, particularly in premenopausal women. Older age and use of hormone replacement therapy were related to the risk of HER-2 overexpressing breast cancer. Our data suggest a significant heterogeneity in association of traditional breast cancer risk factors and tumor subtypes.     

The impact of serum albumin and serum protein levels on POSSUM score of patients with proximal femur fractures

BackgroundPOSSUM was developed to predict risk-adjusted mortality and morbidity rates for surgical procedures. We evaluated the impact of serum albumin and serum protein levels on POSSUM scores.MethodsMedical files of 2269 patients operated for proximal femur fractures were reviewed. Preoperative serum albumin levels were available for 387 patients (mean 35.1 g/l, range 22–49) and serum protein levels for 279 patients (mean 61.6 g/l, range 40–86).ResultsSerum albumin and protein levels were inversely associated with mortality in multivariate models (albumin, OR = 0.89, p = 0.009; protein, OR = 0.92, p = 0.009) and in composite outcome models as well (albumin, OR = 0.955, p = 0.219, protein, OR = 0.94, p = 0.014). The area under the curve (AUC) for POSSUM prediction of mortality (n = 1770) was 0.632 (95% CI: 0.580–0.684, p < 0.001). The AUC for a model including serum protein levels was 0.742 (95% CI: 0.649–0.834, p < 0.001). Hospitalisation time was longer for patients with lower serum proteins levels (p = 0.045), with an inverse correlation (Pearson correlation −0.164, p = 0.011).ConclusionsLower preoperative serum albumin and serum protein levels were associated with increased risk for mortality, increased hospitalisation time and poorer outcomes in patients operated for proximal femoral fractures. Including those values to POSSUM scores would increase their predictive power.     

HSD11B1 polymorphisms predicted bone mineral density and fracture risk in postmenopausal women without a clinically apparent hypercortisolemia

IntroductionEndogenous glucocorticoid (GC) may participate in bone physiology, even in subjects with no glucocorticoid excess. 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1) is a primary regulator catalyzing the reduction of inactive cortisone to active cortisol. To elucidate genetic relevance of HSD11B1 variants to vertebral fracture and osteoporosis, we investigated the potential involvement of six HSD11B1 SNPs in postmenopausal women.MethodsAll exons, their boundaries and the promoter region (approximately 1.5 kb) were directly sequenced in 24 individuals. Six polymorphisms were selected and genotyped in all study participants (n = 1329). BMD was measured using dual-energy X-ray absorptiometry.ResultsHSD11B1 + 16374C>T and + 27447G>C were associated with reduced vertebral fracture risk (p = 0.016 and 0.032, respectively). Two of these (LD block2) in intron 5 (rs1000283 and rs932335) were significantly associated with bone mineral density (BMD) at the femoral neck (p = 0.00005 and 0.0002, respectively). Specifically, HSD11B1 + 16374C>T and + 27447G>C polymorphisms were associated with higher BMD values of the femoral neck in multiple comparison (p = 0.0002 and 0.0004, respectively) and Bonferroni corrected significance level (97% power). Consistent with these results, HSD11B1-ht21 and -ht22 comprising both SNPs also showed the evidence of association with BMD values of the femoral neck (p_domiant = 0.0002 and p_recessive = 0.00005, respectively).ConclusionOur results provide preliminary evidence supporting an association of HSD11B1 with osteoporosis in postmenopausal women. Also, these findings demonstrate that + 16374C>T polymorphism may be useful genetic markers for bone metabolism.     

The impact of osteoporosis and vertebral compression fractures on mortality and association with pulmonary function in COPD: A meta-analysis

ObjectiveOsteoporosis is highly prevalent among patients with chronic obstructive pulmonary disease (COPD) and most commonly presents as a vertebral compression fracture (VCF). Our objective was to quantify the effect of osteoporosis and VCFs on the mortality and pulmonary function tests (PFTs), such as forced expiratory volume in 1 second (FEV₁) and forced vital capacity (FVC), of patients with COPD.MethodsA PubMed/Medline search was conducted using the search terms “chronic obstructive pulmonary disease”, “osteoporosis” and “vertebral compression fracture”. Meta-analyses were conducted to evaluate the differences in mortality and PFTs between patients with COPD with and without osteoporosis or VCFs, according to PRISMA guidelines. PROSPERO registration: CRD42019120335.ResultsOf the 896 abstracts identified, 27 studies describing 7662 patients with COPD of which 1883 (24.6%) had osteoporosis or VCFs, were included. Random effects model analysis demonstrated that patients with COPD and osteoporosis or VCFs had an increased OR for mortality of 2.40 (95% CI: 1.24; 4.64, I² = 89%, P < 0.01), decreased FEV₁/FVC with a mean difference of ?4.80% (95% CI: ?6.69; ?2.90, I² = 83%, P < 0.01) and decreased FEV₁, with a mean difference of ?4.91% (95% CI: ?6.51; ?3.31, I² = 95%, P < 0.01) and ?0.41 L (95% CI: ?0.59; ?0.24, I² = 97%, P < 0.01), compared to control subjects. Apart from FEV₁ (liters) in subgroup 1 (P = 0.06), all subgroup analyses found significant differences between groups, as did sensitivity analysis of low risk of bias studies.ConclusionOsteoporosis and VCFs are associated with a significant reduction in survival and pulmonary function among patients with COPD.     

Association between IVS3 + 17T/C CD28 gene polymorphism and the acute kidney allograft rejection

CD28 is a costimulatory molecule which plays an important role in T cell-mediated immune response and transplantation. The aim of the present study was to examine the association between the IVS3 + 17T/C (rs3116496:T/C) polymorphism in the CD28 gene and the development of delayed renal graft function (DGF), as well as the acute rejection and chronic allograft nephropathy. A total of 270 recipients of the first renal transplants were included in the study. SNP within the CD28 gene was genotyped using TaqMan genotyping assay.Acute rejection was diagnosed in 21.74% of the carriers of the TT genotype, 33.33% of CT carriers and 60.00% of CC homozygotes. The odds of acute rejection were statistically significantly higher in carriers of the C allele (with CT or CC genotype) compared with TT homozygotes (CC + CT vs TT: OR = 1.93, 95%CI = 1.10–3.39, p = 0.026). There were no statistically significant associations between CD28 gene polymorphism and DGF as well as chronic allograft nephropathy.The results of our study suggest an association between IVS3 + 17T/C polymorphism in the CD28 gene and acute kidney allograft rejection.