C-reactive protein (CRP) levels in systemic lupus erythematosus (SLE)

Summary CRP levels in 194 serum samples from 43 SLE patients were measured. Patients with inactive disease have levels below 10 g/ml; patients with active SLE have higher levels, but never over 50 g/ml. In the presence of infection or inflammatory processes, regardless of the activity of SLE, the levels are significantly higher (p<0.05), and well over 50 g/ml. Both active SLE patients and inactive SLE patients with local infections have levels between 10 g/ml and 50 g/ml. In this situation, the presence of anti-DNA antibodies strongly suggests disease activity (82% versus 9%, p<0.05). The clinical and physiopathological meaning of these findings is discussed.     

Dynamics of serum C-reactive protein (CRP) level and cosmophysical activity

BACKGROUND: C-reactive protein (CRP), an acute phase reactant, plays an important part in the investigation of the role of inflammation in pathology. Many cardiovascular events show significant associations with various cosmophysical parameters. The aim of this study was to investigate the relationship between the level of CRP and the levels of solar, geomagnetic (GMA), and cosmic ray activity. METHODS: The results of 25,399 serum CRP tests carried out over a 3-year period were compared with the monthly and daily levels of solar, geomagnetic, and cosmic ray activity during the same period. The cosmophysical data were obtained from the National Oceanic Atmospheric Administration (NOAA) in the U.S. and from the Russian Academy of Science. RESULTS: On a monthly basis, CRP levels showed no correlation with GMA (n=36, r=0.258, p=0.13), but there was a significant inverse relationship with neutron activity (r=-0.35, p=0.03). For the daily comparisons, CRP levels were significantly correlated with GMA (n=1057, r=0.97, p=0.02), and there was a significant inverse relationship with neutron activity (r=-0.97, p=0.025). Daily neutron activity was higher on days with CRP levels of 0-1.0 mg/dl (n=289) and above1.0-1.5 mg/dl (n=1213) than on days with higher CRP values (>1.5; n=23,897; p<0.0001). CONCLUSION: The level of serum CRP, in addition to its association with inflammation, is related to the daily level of GMA and inversely to the level of neutron activity.     

Diet quality is associated with circulating C-reactive protein but not irisin levels in humans

Objective

Adherence to a healthy diet has been shown to decrease the incidence of obesity and associated comorbidities. C-reactive protein (CRP) is an established inflammatory marker and irisin was recently identified as a molecule which may play a role in energy regulation and obesity but whether diet alters irisin levels remains unknown. We aimed to investigate the association between circulating irisin, leptin, and CRP levels and dietary quantity and quality using the Alternate Healthy Eating Index (AHEI) and the Alternate Mediterranean Diet Score (aMED).

Materials/Methods

The study evaluated dietary data and biomarker levels of 151 participants between 2009 and 2011 (71 male vs. 80 female, over 35 years old, obese 43.7%). AHEI and aMED scores were calculated based on data derived from self-administered 110-item food-frequency questionnaires estimating usual nutrient intake over the past year. Cross-sectional associations between dietary quantity, quality, body composition by bioelectric impedance, and biomarker levels including irisin, leptin, and CRP after fasting were assessed.

Results

CRP, but not irisin, was negatively correlated with AHEI (r = − 0.34) and aMED (r = − 0.31). Irisin was positively correlated with BMI (r = 0.22), fat mass (r = 0.21), waist circumference (r = 0.24), waist–hip ratio (r = 0.20), leptin (r = 0.32), and CRP (r = 0.25). Participants with the highest AHEI scores tended to have 11.6% lower concentrations of irisin (P for trend = 0.09), but they were not significant after adjustment for potential confounders. Better diet quality was associated with lower CRP concentrations (P for trend = 0.02) in multivariate model. Percentage of energy from carbohydrate was inversely associated with CRP.

Conclusions

Unlike CRP, irisin is not associated with dietary quality or quantity.     

Follistatin-related protein gene (FRP) is expressed in the synovial tissues of rheumatoid arthritis, but its polymorphisms are not associated with genetic susceptibility

OBJECTIVE: To examine the expression level and function of follistatin-related protein gene (FRP, also referred to as FSTL1) in rheumatoid arthritis (RA), and possible association of its polymorphisms with genetic susceptibility to RA. METHODS: FRP mRNA expression levels in the synovial tissues from 10 patients with RA and 5 patients with OA were measured using real-time RT-PCR. Effects on the growth of synovial cells were evaluated by stably introducing FRP cDNA into a rheumatoid synovial cell line, E11. Screening of genomic DNA variations was done using DNA from 12 patients with RA and 12 healthy individuals by direct sequencing. Genotypes at the detected polymorphic sites were determined in 224 patients with RA and 220 healthy individuals using PCR-single strand conformation polymorphism. RESULTS: FRP mRNA was overexpressed in synovial tissues from RA patients by 2.3-fold as compared with those from OA. A rheumatoid synovial cell line (E11) transfected with FRP exhibited reduced proliferation, probably mediated by secreted FRP molecule. 16 genomic variations were identified, among which 4 were polymorphisms within the promoter region and exons, and the remainder were either rare variations or intronic polymorphisms. Genotyping of 4 polymorphic sites did not reveal statistically significant association with the susceptibility to RA. CONCLUSION: FRP mRNA is overexpressed in RA synovium, the product of which exerts inhibitory activity on synovial cell growth. Although new polymorphic sites were identified, they were not associated with susceptibility to RA, suggesting that overexpression of FRP is secondarily caused by synovial environment of RA.     

Integrin alpha V polymorphisms and haplotypes in a Korean population are associated with susceptibility to chronic hepatitis and hepatocellular carcinoma

Background/Aims: Integrins are cell surface receptors for extracellular matrix (ECM) proteins that initiate signalling pathways that modulate proliferation, survival, invasion or metastasis. Consequently, integrins are potential targets for the treatment of cancer. In this study, we investigated whether single nucleotide polymorphisms (SNPs) in integrin α_V (ITGAV) in a Korean population were associated with chronic hepatitis B virus (HBV) infection and HBV‐infected hepatocellular carcinoma (HCC). Patients and Methods: Thirteen ITGAV SNPs in 111 cases of chronic HBV infection, 86 cases of HBV‐infected HCC and 107 cases of acute self‐limited HBV infection were genotyped using Illumina's Sentrix array matrix (SAM) chip. Results: The ITGAV intron SNPs rs9333289 and rs11685758, the 3′‐untranslated region SNP rs1839123 and haplotype 3 (T–T–A) were associated with enhanced susceptibility to HBV‐infected HCC (OR=1.75–2.42; P=0.02–0.05), while the intron SNP rs2290083 was associated with both chronic infection and HBV‐infected HCC (OR=1.73–2.01; P=0.01–0.04). In addition, both rs2290083 and ht1 (C–C–G) were associated with the age at which chronic infection occurred, as determined by Cox relative hazard analysis (RH=1.39–1.62, P=0.04–0.01) Conclusion: ITGAV SNPs and haplotypes may be genetic factors that increase the susceptibility of Koreans to chronic HBV infection and HBV‐infected HCC.     

Platelet activating factor-acetylhydrolase (PAF-AH) activity and HDL levels, but not PAF-AH gene polymorphisms, are associated with successful aging in Sicilian octogenarians

BACKGROUND AND AIMS: Aging is associated with an increased risk of developing atherosclerosis. Subjects over 80 years of age without cardiovascular disease provide a model to investigate the protective factors increasing their resistance to atherosclerotic disease. Platelet-activating factor acetylhydrolase (PAF-AH) is an enzyme associated with low density lipoprotein (LDL) and high density lipoprotein (HDL) inactivating platelet-activating factor (PAF) and preventing LDL oxidation by hydrolysis of oxidized phospholipids. The aim of the present study was to evaluate the contribution of the PAFAH gene Arg92His, Ile198Thr and Ala379Val polymorphisms to resistance toward developing cardiovascular events in healthy Sicilian octogenarians. METHODS: Distribution of PAF-AH genotypes and activity, and biochemical parameters, were compared between 100 octogenarians and 200 healthy adults. RESULTS: The individuals in the elderly group displayed significantly higher levels of HDL-C (p<0.001) and plasma (p<0.001) and HDL (p<0.001) PAF-AH activity. Analysis of PAFAH genotype distributions showed no significant differences between octogenarians and controls. No differences among PAF-AH genotypes with respect to plasma and HDL PAF-AH activity were found in either group. CONCLUSIONS: Our results provide no evidence of a significant association between the PAF-AH gene Arg92His, Ile198Thr and Ala379Val polymorphisms and successful aging in Sicilians. They also emphasize that, in these subjects, aging is characterized by increased levels of PAF-AH activity and HDL-C.     

High levels of antibodies against Clq are associated with disease activity and nephritis but not with other organ manifestations in SLE patients.

OBJECTIVE: Serum concentration of antibodies to C1q (C1qAb) has been reported to be elevated in a high percentage of patients with systemic lupus erythematosus (SLE). The associations of high C1qAb levels with different clinical manifestations and the activity of the disease, however, are not definitely understood. METHODS: We measured the levels of IgG type C1qAb in the sera of 137 patients with SLE using an ELISA method. RESULTS: Serum concentrations of C1qAb were found to be higher (p < 0.0001) in SLE patients than in healthy controls. High titer (> 66 AU/ml) C1qAb was found in 40/137 (29.2%) SLE patients, and 4/192 (2.1%) healthy controls (p < 0.0001). A strong negative correlation (R = -0.4, p < 0.0001) between the age of the patients and the C1qAb titers could be detected. C1qAb levels in clinically active SLE patients significantly (p < 0.0001) exceeded those measured in the sera of patients in the inactive stage of the disease. A significant positive correlation was detected between C1qAb levels and the laboratory activity markers (anti-DNA, low C3 level) of the disease. We found a significant negative correlation between levels of C1qAb and a negative acute phase protein, alpha2-HS-glycoprotein. Renal involvement was present in 11/40 (27.5%) and 11/97 (11%) of the patients with high and low titers of C1qAb, respectively (p = 0.038). The prevalence of other organ manifestations was, however, the same in the patients with or without high titer C1qAb. CONCLUSION: These findings indicate that C1qAb measurement is a useful method for detecting the activity of SLE and predicting renal manifestations, but not other organ involvement in the disease.     

Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis

INTRODUCTION Methylation of gene regulatory elements is a well-documented epigenetic change that can lead to gene inactivation. Human gastric carcinogenesis is suggested to be associated with the decrease of total genomic DNA methylation, hypomethylation …     

Correlation between interleukin-6 promoter and C-reactive protein (CRP) polymorphisms and CRP levels with the Mainz Severity Score Index for Fabry disease

Summary Objectives: Fabry disease is a multisystem disorder with phenotypic heterogeneity only partially explained by genotype. Elevated interleukin-6 (IL-6) plasma levels and C-reactive protein (CRP) serum levels are associated with increased risk and worse outcome of ischaemic events, a serious prognostic sign in Fabry disease. Methods: 56 patients (34 hemizygous males, 22 females; 5 children) were studied. A promoter polymorphism −174G > C of the IL-6 gene associated with serum IL-6 levels was compared with the Mainz Severity Score Index (MSSI) in patients with Fabry disease. CRP levels and polymorphism 1059 G > C were evaluated as markers of inflammation to ascertain the possibility of an inflammatory mechanism of IL-6. Nonparametric ANOVA, Fisher’s exact, Bonferroni, and Hardy–Weinberg (HW) statistics were used. Results: Mean age of adults = 42 (range 26–58) years; 29 patients received enzyme therapy (ERT). Mean total MSSI = 26.7 (range 14.2–39.2) points, i.e. moderate disease, but females were lower (total 23.4 ± 12.6 vs 32.2 ± 13.6). Controls but not patients were in HW equilibrium. Significant correlation existed between all sub-scores of the MSSI and IL-6 genotypes in females but only with three MSSI sub-scores for males. The IL-6 C/C genotype was significantly correlated with the neurological, general and total MSSI sub-scores, generally twofold higher. There were no statistically significant correlations with CRP levels/polymorphisms and MSSI sub-scores nor with IL-6 polymorphisms. CRP levels decreased after ERT in patients with IL-6 G/G or G/C genotypes but increased in patients with C/C (p = 0.003). Conclusions: The prevalence of the IL-6 C allele significantly influences MSSI, i.e. clinical severity, especially in females. This is unrelated to IL-6 as a pro-inflammatory marker as demonstrated by lack of correlations with CRP levels and genotypes. IL-6 −174 polymorphic C allele may be a prognostic marker in Fabry disease, especially in females. Competing interests: None declared     

ITGA1 polymorphisms and haplotypes are associated with gastric cancer risk in a Korean population

AIM:To evaluate the association between the geneticpolymorphisms and haplotypes of the ITGA1 gene and the risk of gastric cancer.METHODS:The study subjects were 477 age-and sex-matched case-control pairs.Genotyping was performed for 15 single nucleotide polymorphisms(SNPs)in ITGA1.The associations between gastric cancer and these SNPs and haplotypes were analyzed with multivariate conditional logistic regression models.Multiple testing corrections were carried out following methodology for controlling the false discovery rate.Gene-based association tests were performed using the versatile gene-based association study(VEGAS)method.RESULTS:In the codominant model,the ORs for SNPs rs2432143(1.517;95%CI:1.144-2.011)and rs2447867(1.258;95%CI:1.051-1.505)were statistically significant.In the dominant model,polymorphisms of rs1862610 and rs2447867 were found to be significant risk factors,with ORs of 1.337(95%CI:1.029-1.737)and 1.412(95%CI:1.061-1.881),respectively.In the recessive model,only the rs2432143 polymorphism was significant(OR=1.559,95%CI:1.150-2.114).The C-C type of ITGA1 haplotype block 2 was a significant protective factor against gastric cancer in the both codominant model(OR=0.602,95%CI:0.212-0.709,P=0.021)and the dominant model(OR=0.653,95%CI:0.483-0.884).The ITGA1 gene showed a significant gene-based association with gastric cancer in the VEGAS test.In the dominant model,the A-T type of ITGA1 haplotype block 2 was a significant risk factor(OR=1.341,95%CI:1.034-1.741).SNP rs2447867 might be related to the severity of gastric epithelial injury due to inflammation and,thus,to the risk of developing gastric cancer.CONCLUSION:ITGA1 gene SNPs rs1862610,rs2432143,and rs2447867 and the ITGA1 haplotype block that includes SNPs rs1862610 and rs2432143 were significantly associated with gastric cancer.     

Renin polymorphisms and haplotypes are associated with blood pressure levels and hypertension risk in postmenopausal women

BACKGROUND: Renin is a key protein of the renin-angiotensin system involved in the physiological control of blood pressure; the renin gene is therefore a candidate for essential hypertension in humans. We tested the association between polymorphisms and haplotypes of the renin gene and the risk of hypertension and blood pressure levels in two Spanish populations. METHODS: Two population-based studies from different regions of Spain were performed. Study A included 1502 individuals (748 women) 40-70 years old, and Study B included 670 women 45-70 years old. Fourteen polymorphisms of the renin gene were selected based on position, spacing, heterozygosity (> 10% for the minor allele frequency) and previous information, and were assessed by SNPlex. RESULTS: Genotype GG of the rs5707 polymorphism was significantly associated with blood pressure levels (P = 0.005) and with the risk of having hypertension (odds ratio, 6.16; 95% confidence interval, 1.19-31.8) in women 40-70 years old from study A, but not the men. This association was also present in the women of study B (P < 0.001 for blood pressure values; odds ratio, 2.11 and 95% confidence interval, 1.07-4.17 for hypertension). Two haplotypes defined by five selected polymorphisms were associated with increased risk of hypertension in these aged women. CONCLUSION: Polymorphisms of the renin gene were associated with blood pressure levels and risk of hypertension in women over 40 years old. The interaction between the potential functional impact of this genetic background and the estrogen fall could explain the association in women of this age group.     

The haplotypes of TNFRSF17 polymorphisms are associated with colon cancer in a Korean population

Purpose

We previously found that the haplotypes of TNFRSF17 single nucleotide polymorphisms (SNPs) were associated with the susceptibility to inflammatory bowel disease on Korean population. The present study aimed to investigate whether the polymorphisms in the TNFRSF17 gene are associated with susceptibility to colorectal cancer (CRC).

Methods

Genotype analysis in the TNFRSF17 SNPs was performed by high-resolution melting and TaqMan probe analysis, and the genotype and allele frequencies of TNFRSF17 SNPs were compared between the CRC patients and the healthy controls. The haplotype frequencies of TNFRSF17 for multiple loci were estimated using the expectation maximization algorithm.

Results

Although, the genotype and allelic frequencies of these SNPs, in the colon cancer and rectal cancer patients, were not significantly different from those in the healthy controls, the genotype and allele frequency of g.2493G>A was significantly different between the healthy controls and the right colon cancer patients (P?=?0.014 and 0.004, respectively). Moreover, the haplotypes frequencies in the healthy controls were significantly different from those in the colon cancer patients.

Conclusion

Our results suggest that TNFRSF17 may be a candidate gene associated with the pathogenesis of colon cancer, and the haplotypes of the TNFRSF17 polymorphisms might be one of the markers for colon cancer susceptibility.     

Thrombin activatable fibrinolysis inhibitor gene polymorphisms are associated with antigenic levels in the Asian-Indian population but may not be a risk for stroke

Thrombin activatable fibrinolysis inhibitor [carboxypeptidase B2 (plasma), CPB2] is a basic carboxypeptidase, which inhibits fibrinolysis by cleaving the C-terminal lysine residues on plasmin-modified partially degraded fibrin. Plasma CPB2 concentrations have been reported to be under the control of numerous single nucleotide polymorphisms located in the regulatory and coding regions of the gene encoding CPB2 (CPB2). High functional CPB2 levels have been found to be associated with an increased risk for ischemic stroke. The present study investigated CPB2 antigen levels and associated CPB2 polymorphisms in an acute onset non-cardioembolic stroke population compared with an age- and sex-matched healthy control population. This is, to the best of our knowledge, the first such study done in an Asian Indian population. CPB2 antigen levels were significantly associated with the disease phenotype (P < 0.001) and with CPB2 polymorphisms (P < 0.001). The haplotypes generated on analysis of the genotypic data accounted for 21% of the natural variation in the CPB2 antigenic levels. However none of the haplotype combinations generated showed any association with disease phenotype and therefore could not explain for the difference in CPB2 antigen levels between cases and controls.     

Single-nucleotide polymorphisms in the SPARC gene are not associated with susceptibility to scleroderma

OBJECTIVE: SPARC (secreted protein, acidic and rich in cysteine) is a matricellular protein that modulates cell-cell and cell-extracellular matrix interactions. SPARC expression is restricted mainly to sites of tissue remodelling and wound repair, and is prominent in fibrotic disorders. Single-nucleotide polymorphisms (SNPs) in the SPARC gene are reportedly linked to scleroderma in four ethnic groups: Choctaw Indians, Caucasians, African Americans and Mexican Americans. We set out to reproduce and to positionally clone these disease associations in a set of UK Caucasian scleroderma patients and ethnically matched controls. METHODS: One hundred and twenty-one scleroderma subjects and 200 controls were genotyped by polymerase chain reaction with sequence-specific primers differing only in the 3' nucleotide corresponding to each allele of the biallelic SNPs. Scleroderma patients were analysed against controls and on the basis of their fibrosing alveolitis status as judged by high-resolution computed tomography evaluation and the extent of cutaneous involvement. RESULTS: Eight biallelic SNPs were genotyped: three from the last untranslated exon, which had been described previously, and an additional five novel SNPs: two in the promoter region, one in exon three and two in the 3' untranslated region. Six major haplotypes were constructed across all eight SNP positions. No significant differences in genotype, allele or haplotype frequency were observed between scleroderma and controls or within scleroderma subgroups. CONCLUSIONS: SNPs in the SPARC gene are not associated with susceptibility to scleroderma. This research adds to the genetic knowledge of the SPARC gene by identifying five novel SNPs spanning the whole gene and inserting these within the context of clearly defined haplotypes.