Influence of the CYP2J2 Gene Polymorphisms on Chronic Obstructive Pulmonary Disease Risk in the Chinese Han Population

IntroductionCytochrome P450 (CYP) 2J2 is a major enzyme that controls epoxyeicosatrienoic acids biosynthesis, which may play a role in chronic obstructive pulmonary disease (COPD) development. In this study, we aimed to assess the influence of CYP2J2 polymorphisms with COPD susceptibility.Material and methodsA case–control study enrolled 313 COPD cases and 508 controls was to investigate the association between CYP2J2 polymorphisms and COPD risk. Agena MassARRAY platform was used to genotype CYP2J2 polymorphisms. Odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the association between CYP2J2 polymorphisms and COPD risk.ResultsWe observed rs11207535 (homozygote: OR = 0.08, 95%CI = 0.01–0.96, p = 0.047; recessive: OR = 0.08, 95%CI = 0.01–0.94, p = 0.044), rs10889159 (homozygote: OR = 0.08, 95%CI = 0.01–0.92, p = 0.043; recessive: OR = 0.08, 95%CI = 0.01–0.90, p = 0.040) and rs1155002 (heterozygote: OR = 1.63, 95%CI = 1.13–2.36, p = 0.009; dominant: OR = 1.64, 95%CI = 1.15–2.35, p = 0.006; additive: OR = 1.45, 95%CI = 1.09–1.92, p = 0.011) were significantly associated with COPD risk. Allelic tests showed T allele of rs2280274 was related to a decreased risk of COPD and T allele of rs1155002 was associated with an increased COPD risk. Stratified analyses indicated the effects of CYP2J2 polymorphisms and COPD risk were dependent on gender and smoking status (p < 0.05). Additionally, two haplotypes (A_rs11207535C_rs10889159T_rs1155002 and A_rs11207535C_rs10889159C_rs1155002) significantly decreased COPD risk.ConclusionIt suggested CYP2J2 polymorphisms were associated with COPD susceptibility in the Chinese Han population.     

Polymorphisms in inflammation associated genes ALOX15 and IL-6 are associated with bone properties in young women and fracture in elderly

PurposeALOX12 and ALOX15 encode arachidonate lipoxygenases which produce lipid metabolites involved in inflammatory processes. Metabolites generated by ALOX12 and ALOX15 can activate the expression of the potent pro-inflammatory cytokine IL-6, and produce endogenous ligands for PPARG. In this study, polymorphisms in ALOX12, ALOX15, IL6 and PPARG were investigated for association with bone properties in young and elderly Swedish women.MethodsThree SNPs in ALOX12, five in ALOX15, one each in IL6 and PPARG were genotyped in the cohorts PEAK-25 (n = 1061 women; all 25 y) and OPRA (n = 1044 women; all 75 y). Bone mineral density (BMD) and quantitative ultrasound (QUS) were analyzed in both cohorts; trabecular bone score (TBS) in PEAK-25; bone loss, fracture incidence and serum C-reactive protein (CRP) were assessed in OPRA.ResultsIn the elderly women ALOX15 (rs2619112) was associated with CRP levels (p = 0.004) and incident fracture of any type (p = 0.014), although not with BMD or ultrasound. In young women, carrying the common T allele (ALOX 15 rs748694) was associated with lower QUS values (p = 0.002–0.006). The IL6 SNP was associated with lower BMD in PEAK-25 (femoral neck p = 0.034; hip p = 0.012). TBS was not associated with variation in any gene. Variants in the ALOX12 and PPARγ were not associated with BMD in either cohort.ConclusionsThis study suggests that variation in inflammation related genes ALOX15 and IL6 was associated with bone microarchitecture and density in young adult women, but appears to be less important in the elderly, despite an observed association with CRP as a marker of inflammation and incident fracture.     

Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males

Compressive strength index (CSI) is a newly established index for predicting hip fracture, the most serious consequence of osteoporosis. Appendicular lean mass (ALM), which influences skeletal strength of the lower limbs, is another trait associated with the risk of hip fracture. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both CSI and ALM. In our discovery sample of 1627 unrelated Chinese subjects (802 males and 825 females), we scanned 909,509 SNPs using the Affymetrix Human Genome SNP 6.0 genotyping array. We successfully replicated our results in a sample of 2286 Caucasian subjects (558 males and 1728 females). The results indicated that five SNPs (rs174583, rs174577, rs174549, rs174548, rs7672337) in the FADS1, FADS2, and DCHS2 genes had significant bivariate associations with CSI and ALM in male subjects for both the GWAS discovery (with P < 8.42 × 10^? 6) and the Caucasian sample (with P < 0.07). We performed further replication analysis in a 2nd Caucasian sample with 501 Caucasian male subjects, using Affymetrix 500 k arrays, and found that two of the above SNPs (rs174548 and rs174549, P = 0.07) had bivariate associations with both CSI and ALM in males; the other 3 SNPs were not typed with the 500 k array. The above findings suggest that the 3 genes, FADS1, FADS2, and DCHS2, containing these SNPs might play dual roles influencing both CSI and ALM in males. Our findings provide new insights into our understanding of the genetic basis of bone metabolism and the pathogenesis of osteoporosis.     

Bivariate genome-wide association study suggests fatty acid desaturase genes and cadherin DCHS2 for variation of both compressive strength index and appendicular lean mass in males

Compressive strength index (CSI) is a newly established index for predicting hip fracture, the most serious consequence of osteoporosis. Appendicular lean mass (ALM), which influences skeletal strength of the lower limbs, is another trait associated with the risk of hip fracture. In this study, we performed a bivariate genome-wide association study (GWAS) to identify new candidate genes responsible for both CSI and ALM. In our discovery sample of 1627 unrelated Chinese subjects (802 males and 825 females), we scanned 909,509 SNPs using the Affymetrix Human Genome SNP 6.0 genotyping array. We successfully replicated our results in a sample of 2286 Caucasian subjects (558 males and 1728 females). The results indicated that five SNPs (rs174583, rs174577, rs174549, rs174548, rs7672337) in the FADS1, FADS2, and DCHS2 genes had significant bivariate associations with CSI and ALM in male subjects for both the GWAS discovery (with P < 8.42 × 10^− 6) and the Caucasian sample (with P < 0.07). We performed further replication analysis in a 2nd Caucasian sample with 501 Caucasian male subjects, using Affymetrix 500 k arrays, and found that two of the above SNPs (rs174548 and rs174549, P = 0.07) had bivariate associations with both CSI and ALM in males; the other 3 SNPs were not typed with the 500 k array. The above findings suggest that the 3 genes, FADS1, FADS2, and DCHS2, containing these SNPs might play dual roles influencing both CSI and ALM in males. Our findings provide new insights into our understanding of the genetic basis of bone metabolism and the pathogenesis of osteoporosis.     

Risk stratification using anti-citrullinated peptide antibodies (ACPA) in polyarticular subtypes of juvenile idiopathic arthritis in adulthood

ObjectivesPolyarticular juvenile idiopathic arthritis (pJIA) is a subset of juvenile idiopathic arthritis (JIA), divided into two subtypes according to the presence of rheumatoid factor: pJIA without rheumatoid factor (pJIA RF-) and pJIA with positive rheumatoid factor (pJIA RF + ), this latter is characterised with more structural damage. Anti-citrullinated peptide antibodies (ACPA) are often associated with RF. The respective performance of ACPA versus RF in structural outcome in pJIA, and in particular in adulthood pJIA remains unknown. Therefore, the aim of this study was to determine whether ACPA could be of value to assess structural damage in pJIA persisting in adulthood.MethodsPatients with pJIA and available data for ACPA, RF and X-ray were included retrospectively. Structural damage was assessed by two independent blinded investigators using Sharp Van Der Heijde scores.Results56 pJIA adult patients were included: 62% (35/56) had pJIA RF+ and 38% (21/56) pJIA RF-. ACPA positivity in pJIA was significantly associated with presence of RF (96% vs 26%, P < 0.001). RF positivity was significantly associated with higher Sharp van Der Heijde erosion and total scores (respectively P < 0.01 and P < 0.05). There were higher Sharp Van Der Heijde erosion, joint space narrowing and total scores in the pJIA ACPA+ subgroup than in the pJIA ACPA- subgroup, although there was no statistical significance. However, when adjusted on disease duration, pJIA ACPA+ patients had significantly higher erosion and total scores than pJIA ACPA- patients (P < 0.05), and pJIA ACPA+ patients required more bDMARDs than pJIA ACPA- patients (P < 0.05). Moreover, pJIA patients with high Sharp van Der Heijde joint space narrowing and total scores had significantly higher ACPA levels (P < 0.01). A correlation was identified between ACPA levels and Sharp van Der Heijde total score (r = 0.54, P < 0.05). In the pJIA RF+ subgroup the presence of ACPA was associated with additional structural damage compared to no ACPA: sharp Van Der Heijde erosion, joint space narrowing and total scores were higher in the pJIA RF+ ACPA+ subgroup than in the pJIA RF+ ACPA- subgroup although these results did not reach significance.ConclusionOur results suggest that pJIA RF+ ACPA+ adult patients may have a more severe articular phenotype than pJIA RF+ ACPA- patients. ACPA could bring an additional value to RF for pJIA patients regarding structural damage. Altogether our results show that RF and ACPA are associated with structural damage measured by Sharp Van Der Heijde score in pJIA persisting in adulthood.     

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.     

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.     

Induction of the chemokine IL-8/Kc by the articular cartilage: Possible influence on osteoarthritis

PurposeIL-8 and its murine equivalent keratinocyte chemoattractant (Kc), chemokines produced by chondrocytes, contribute to the pathophysiology of osteoarthritis. However, the mechanisms leading to their production are poorly known. We aimed to investigate whether mechanical (compression), inflammatory (IL-1β) and metabolic (visfatin) stresses may induce the release of Kc when applied on murine cartilage.MethodsMouse cartilage explants were subjected to intermittent compression for 4, 6 and 24 h. Primary cultures of immature murine articular chondrocytes were obtained by enzymatic digestion of articular cartilage from 6-days-old newborns mice. The effect of compression, IL-1β (10, 50, 100 pg/mL) and of visfatin (5 μg/mL) on the release of Kc was assessed by ELISA. IL-8 levels in conditioned media from human OA joint tissues (cartilage or synovium) were also assessed.ResultsIn comparison with non-compressed explants, loading increased Kc release of 3.2-, 1.9- and 2.0-fold at 4, 6 and 24 h respectively (P < 0.004, n = 9). IL-1β triggered an increase of Kc release by primary cultured chondrocytes of 4.1-, 15.5- and 35.2-fold at 10, 50 and 100 pg/mL of IL-1β respectively (P < 0.05, n = 4). Likewise, visfatin (5 μg/mL) induced an increase in Kc release of 56.5 ± 25.2 fold (P = 0.002, n = 6). IL-8 was released in conditioned media by synovium as well as by cartilage.ConclusionWe show for the first time that IL-8/Kc is highly responsive to mechanical, inflammatory and metabolic stresses, strengthening the hypothesis that IL-8/Kc could be added to the cytokines which may have a deleterious impact in osteoarthritis.     

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.     

Genome-wide association meta-analyses identified 1q43 and 2q32.2 for hip Ward's triangle areal bone mineral density

Aiming to identify genomic variants associated with osteoporosis, we performed a genome-wide association meta-analysis of bone mineral density (BMD) at Ward's triangle of the hip in 7175 subjects from 6 samples. We performed in silico replications with femoral neck, trochanter, and inter-trochanter BMDs in 6912 subjects from the Framingham heart study (FHS), and with forearm, femoral neck and lumbar spine BMDs in 32965 subjects from the GEFOS summary results. Combining the evidence from all samples, we identified 2 novel loci for areal BMD: 1q43 (rs1414660, discovery p = 1.20 × 10^− 8, FHS p = 0.05 for trochanter BMD; rs9287237, discovery p = 3.55 × 10^− 7, FHS p = 9.20 × 10^− 3 for trochanter BMD, GEFOS p = 0.02 for forearm BMD, nearest gene FMN2) and 2q32.2 (rs56346965, discovery p = 7.48 × 10^− 7, FHS p = 0.10 for inter-trochanter BMD, GEFOS p = 0.02 for spine BMD, nearest gene NAB1). The two lead SNPs rs1414660 and rs56346965 are eQTL sites for the genes GREM2 and NAB1 respectively. Functional annotation of GREM2 and NAB1 illustrated their involvement in BMP signaling pathway and in bone development. We also replicated three previously reported loci: 5q14.3 (rs10037512, discovery p = 3.09 × 10^− 6, FHS p = 8.50 × 10^− 3, GEFOS p = 1.23 × 10^− 24 for femoral neck BMD, nearest gene MEF2C), 6q25.1 (rs3020340, discovery p = 1.64 × 10^− 6, GEFOS p = 1.69 × 10^− 3 for SPN-BMD, nearest gene ESR1) and 7q21.3 (rs13310130, discovery p = 8.79 × 10^− 7, GEFOS p = 2.61 × 10^− 7 for spine BMD, nearest gene SHFM1). Our findings provide additional insights that further enhance our understanding of bone development, osteoporosis, and fracture pathogenesis.     

Apolipoprotein m (APOM) levels and APOM rs805297 G/T polymorphism are associated with increased risk of rheumatoid arthritis

ObjectiveTo examine whether the apolipoprotein M (APOM) rs805297 G/T polymorphism is associated with risk of rheumatoid arthritis (RA) in a Chinese population.MethodsWe studied APOM rs805297 G/T gene polymorphism in 520 RA patients, and 520 controls in a Chinese population. Genotyping was done by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The blood plasma concentration of APOM was measured by an enzyme-linked immunosorbent assay in 84 RA patients and 84 controls.ResultsWhen the APOM rs805297 G/T GG homozygote genotype was used as the reference group, the TT or GT/TT genotype was associated with an increased risk for RA (TT vs. GG, adjusted odds ratio 1.76, 95% CI 1.11–2.77, P = 0.016; GT + TT vs. GG, adjusted odds ratio 1.30, 95% CI 1.02–1.67, P = 0.037). The average concentration of APOM in plasma was significantly higher in RA patients compared to controls. Stratification analysis found a significantly increased risk for RA associated with the APOM rs805297 TT genotype among male patients, C-reactive protein (CRP)-positive patients, anticitrullinated protein/peptide antibodies (ACPA) – positive patients, rheumatoid factor (RF) – positive patients, patients with higher levels of the erythrocyte sedimentation rate (ESR), patients with higher DAS28 score and patients with higher functional class compared to the APOM rs805297 GG genotype.ConclusionThese findings suggest that the functional single-nucleotide polymorphism APOM rs805297 G/T variant allele was associated with RA risk.     

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.     

Effect of Th2 type cytokines on hCLCA1 and mucus expression in cystic fibrosis airways

Correlations between expression of interleukin (IL)-9, the calcium-activated chloride channel hCLCA1 and mucus expression in cystic fibrosis (CF) airways have suggested a causal relationship. To verify this hypothesis mucosal tissue from upper airways of CF patients (N = 5) was stimulated with the Th2 type cytokines IL-4, IL-9, or IL-13. Expression of hCLCA1 mRNA and protein as well as mucus and mucin (MUC5AC) gene expression was quantified using real time PCR, immunohistochemistry (hCLCA1) and PAS staining (mucus). Th2 type cytokines significantly increased hCLCA1 protein expression (P < 0.05) whereas increase in hCLCA1 mRNA expression failed to reach statistical significance (P > 0.05). Mucin protein and MUC5AC mRNA expression were not significantly changed (P > 0.05). These data suggest that Th2 type cytokines may increase hCLCA1 expression in CF but may not have a significant effect on mucus expression. Therefore the role of hCLCA1 as a mediator of mucus overexpression in CF has to be questioned.     

Impact of multimorbidity on disease modifying antirheumatic drug therapy in early rheumatoid arthritis: Data from the ESPOIR cohort

ObjectiveMultimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response. The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis, the ESPOIR cohort, and its possible impact on the therapeutic response.MethodsWe included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed. Each patient was assigned scores of binary aMMI (0 = no comorbidity, 1 = at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying antirheumatic drug (DMARD) according to the aMMI. We collected data from the visit preceding the first DMARD initiation and the visit after at least 3 months of treatment. The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.ResultsAnalyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI = 0 or 1, respectively (non-significant), achieved CDAI low disease activity. Similar results were found with counted and weighted aMMI. Therapeutic maintenance was significantly better with binary aMMI = 1 than binary aMMI = 0 (OR at 10 years = 14.0 [CI 95% 3.3–59.4]). Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point.ConclusionIn the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.     

A genetic association study of the CLEC12A gene in rheumatoid arthritis

ObjectiveThe CLEC12A gene codes for an immune inhibitory receptor that maps to 12p13.2. Since an increase in CLEC12A mRNA correlates with rheumatoid factor values greater than 40 IU/ml in rheumatoid fibroblast-like synovial cells, this study assessed the potential of an association between CLEC12A and rheumatoid arthritis (RA) using a phenotype-based approach.MethodsA discovery cohort of Western European ethnicity was genotyped for eight tag single nucleotide polymorphisms. Statistical analyses relied on the transmission disequilibrium test, relative risk and 95% confidence interval (CI) calculations. Observed haplotype frequencies were compared to expected frequencies using a family-based association test. Statistically significant associations were further tested in a second cohort of unrelated West-European RA patients.ResultsAn overtransmission of the C allele of the rs1323461 tag single nucleotide polymorphism was observed (56.6% of allele C transmission, P = 0.046) in the discovery cohort. The relative risk of the AC and CC genotypes when compared to the AA genotype was high (relative risk = 4.08; 95% CI: 1.52–10.95, uncorrected P = 2.1 × 10^?3), particularly in the subgroup of erosive RA (relative risk = 5.27; 95% CI: 1.53–18.19, uncorrected P = 2.1 × 10^?3), both remaining statistically significant after conservative Bonferroni's correction. The CGAGCCGA haplotype was observed more frequently than expected (P = 0.013). In the second cohort, the C allele had a tendency to be more frequent in RA patients (82.4%) than controls (79.2%) (P = 0.069).ConclusionWe report a potential genetic association of CLEC12A with RA. Since CLEC12A encodes for the myeloid inhibitory C-type lectin-like receptor that modulates cytokine synthesis, this receptor may contribute to the pathogenesis of RA.     

Characterization of prostate cancer using T2 mapping at 3 T: A multi-scanner study

Rationale and objectivesTo assess the prostate T2 value as a predictor of malignancy on two different 3 T scanners.Patients and methodsEighty-three pre-prostatectomy multiparametric MRIs were retrospectively evaluated [67 obtained on a General Electric MRI (scanner 1) and 16 on a Philips MRI (scanner 2)]. After correlation with prostatectomy specimens, readers measured the T2 value of regions-of-interest categorized as “cancers”, “false positive lesions”, or “normal tissue”.ResultsOn scanner 1, in PZ, cancers had significantly lower T2 values than false positive lesions (P = 0.02) and normal tissue (P = 2 × 10⁻⁹). Gleason ≥ 6 cancers had similar T2 values than false positive lesions and significantly higher T2 values than Gleason ≥ 7 cancers (P = 0.009). T2 values corresponding to a 25% and 75% risk of Gleason ≥ 7 malignancy were respectively 132 ms (95% CI: 129–135 ms) and 77 ms (95% CI: 74–81 ms). In TZ, cancers had significantly lower T2 values than normal tissue (P = 0.008), but not than false positive findings. Mean T2 values measured on scanner 2 were not significantly different than those measured on scanner 1 for all tissue classes.ConclusionAll tested tissue classes had similar mean T2 values on both scanners. In PZ, the T2 value was a significant predictor of Gleason ≥ 7 cancers.     

The associations between interleukin-1 polymorphisms and susceptibility to ankylosing spondylitis: a meta-analysis

ObjectiveThe aim of this study was to determine whether polymorphisms of interleukin-1 (IL-1) confer susceptibility to ankylosing spondylitis (AS).MethodsThe authors conducted meta-analyses on associations between IL-1 polymorphisms and AS susceptibility, using fixed or random effects models. In order to avoid duplications and data previously subjected to meta-analysis, we performed meta-analysis on studies if new data on IL-1 polymorphisms in AS were reported.ResultsA total of nine studies consisting of 20 separate comparisons of association between IL-1 polymorphisms and AS susceptibility were included in this meta-analysis. These were performed on European, Asian, and Latin American population samples. Meta-analysis revealed a significant association between the 2 allele of the IL-1F10.3 polymorphism (rs3811581) and the risk of developing AS in Europeans (OR = 0.775, 95% CI = 0.605–0.992, P = 0.043). Furthermore, the OR of the 2 allele of IL-1A + 889 (rs1800587) was found to be significantly increased in Europeans with AS (OR = 1.357, 95% CI = 1.085–1.697, P = 0.007). However, meta-analyses of the IL-1B-511, IL-1B + 3953, and ILF7.1 polymorphisms and of the variable numbers of tandem repeats of the IL-1 receptor antagonist gene (IL-1RN VNTR) revealed no association between AS and these polymorphisms.ConclusionsIn addition to the three known IL-1 polymorphisms, rs2856836, rs17561, and rs1894399, found in previous meta-analysis, this meta-analysis shows that the IL-1F10.3 and IL-1A + 889 polymorphisms are associated with the development of AS in Europeans but not in Asians.