Abstract 35: Common Variants in the CRP Promoter are Associated with a High C-reactive Protein Level in Kawasaki Disease

Circulation ◽  
2015 ◽  
Vol 131 (suppl_2) ◽  
Author(s):  
Jae-Jung Kim ◽  
Sin Weon Yun ◽  
Jeong Jin Yu ◽  
Kyung Lim Yoon ◽  
Kyung-Yil Lee ◽  
...  

Kawasaki disease (KD) is an acute self-limiting form of vasculitis that afflicts infants and children and manifests as fever and signs of mucocutaneous inflammation. Children with KD show various laboratory inflammatory abnormalities, such as elevations in their white blood cell (WBC) count, C-reactive protein (CRP) level, and erythrocyte sedimentation rate (ESR). We here performed a genome-wide association study (GWAS) of 178 KD patients to identify the genetic loci that influence 10 important KD laboratory markers: WBC count, neutrophil count, platelet count, CRP, ESR, hemoglobin (Hb), aspartate aminotransferase (AST), alanine aminotransferase (ALT), albumin, and total protein. A total of 165 loci passed our arbitrary stage 1 threshold for replication ( p < 1 * 10 -5 ). Of these, only 2 SNPs (rs12068753 and rs4786091) demonstrated a significant association with the CRP level in replication study of 473 KD patients ( p < 0.05). The SNP located at the CRP locus (rs12068753) demonstrated the most significant association with CRP in KD patients (beta = 4.73 and p = 1.20 * 10 -6 according to the stage 1 GWAS; beta = 3.65 and p = 1.35 * 10 -8 according to the replication study; beta = 3.97 and p = 1.11 * 10 -13 according to combined analysis) and explained 8.1% of the phenotypic variation observed. However, this SNP did not demonstrate any significant association with CRP in the general population (beta = 0.37 and p = 0.1732) and only explained 0.1% of the phenotypic variation in this instance. Furthermore, rs12068753 did not affect the development of coronary artery lesions or intravenous immunoglobulin resistance in KD patients. These results indicate that common variants in the CRP promoter can play an important role in the CRP levels in KD.

2015 ◽  
Vol 5 (9) ◽  
pp. e633-e633 ◽  
Author(s):  
W Myung ◽  
J Kim ◽  
S-W Lim ◽  
S Shim ◽  
H-H Won ◽  
...  

Abstract We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n=711) revealed GWAS significance (P=1.60 × 10-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n=870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P=3.57 × 10-8). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20–0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.


2014 ◽  
Vol 36 (2) ◽  
pp. 438-444 ◽  
Author(s):  
Jae-Jung Kim ◽  
◽  
Sin Weon Yun ◽  
Jeong Jin Yu ◽  
Kyung Lim Yoon ◽  
...  

2020 ◽  
Vol 29 (1) ◽  
pp. 230949902096829
Author(s):  
Christina van Gerven ◽  
Kevin Eid ◽  
Tobias Krüger ◽  
Michael Fell ◽  
Daniel Kendoff ◽  
...  

Purpose: C-reactive protein (CRP) and white blood cell (WBC) count are routine blood chemistry parameters in monitoring infection. Little is known about the natural history of their serum levels in conservative and operative spondylodiscitis treatment. Methods: Pre- and postoperative serum levels of CRP and WBC count in 145 patients with spondylodiscitis were retrospectively assessed. One hundred and four patients were treated by debridement, spondylodesis, and an antibiotic regime, 41 only with a brace and antibiotics. The results of the surgical group were compared to 156 patients fused for degenerative disc disease (DDD). Results: Surgery had a significant effect on peak postoperative CRP levels. In surgically managed patients, CRP peaked at 2–3 days after surgery (spondylodiscitis: pre-OP: 90 mg/dl vs. post-OP days 2–3: 146 mg/dl; DDD: 9 mg/dl vs. 141 mg/dl; p < 0.001), followed by a sharp decline. Although values were higher for spondylodiscitis patients, dynamics of CRP values were similar in both groups. Nonoperative treatment showed a slower decline. Surgically managed spondylodiscitis showed a higher success rate in identifying bacteria. Specific antibiotic treatment led to a more predictable decline of CRP values. WBC did not show an interpretable profile. Conclusion: CRP is a predictable serum parameter in patients with spondylodiscitis. WBC count is unspecific. Initial CRP increase after surgery is of little value in monitoring infection. A preoperative CRP value, and control once during the first 3 days after surgery is sufficient. Closer monitoring should then be continued. Should a decline not be observed, therapy needs to be scrutinized, antibiotic treatment reassessed, and concomitant infection contemplated.


2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Ademola Olusegun Talabi ◽  
Tewogbade Adeoye Adedeji ◽  
Oludayo Adedapo Sowande ◽  
Olusanya Adejuyigbe

Abstract Background The diagnosis of acute appendicitis in children is quite challenging as the rate of negative appendectomy varies between 15 and 57%. Increased utilization of imaging diagnostic facilities in advanced countries seems to have reduced the incidence of operating on normal appendix to a single digit. In low- and middle-income countries, the incidence remains unacceptably high (double digits). Inflammatory markers and scoring systems may be a suitable adjunct to increase diagnostic yield in most third world countries. Thus, the aim of this study was to evaluate the diagnostic value of Alvarado score, white blood cell count, and serum C-reactive protein in children with acute appendicitis. Results The ages of patients ranged between 4 and 15 years with a mean of 11.2 ± 2.8 years. The male to female ratio was 1.4 to 1.0. Nineteen percent of patients had negative appendiceal findings on histological examination. The sensitivity and specificity of Alvarado score, C-reactive protein estimation, total white blood cell count in diagnosing acute appendicitis were 86.4% and 63.2%, 98.8% and 36.8%, and 51.9% and 89.5% respectively. Alvarado score has the highest area under ROC curve analysis 0.824, 95% CI of 0.724 to 0.924 compared with CRP, 0.769. 95% CI of = 0.647 to 0.891 and WBC count, 0.765, 95% CI of 0.643 to 0.887. Both CRP and WBC count showed higher discriminatory values between complicated and uncomplicated appendicitis, p < 0.001. Conclusion Alvarado score outperformed other tests in setting the diagnosis of acute appendicitis. However, none of the tests can be relied on wholly for operative decision. Clinical judgement remains the bedrock for diagnosis and operative management.


2017 ◽  
Vol 16 (2) ◽  
pp. 52-59
Author(s):  
Sotirios Kakavas ◽  
◽  
Aggeliki Papanikolaou ◽  
Evangelos Balis ◽  
Evgenios Metaxas ◽  
...  

Our aim was to prospectively assess the prognostic value of beta2- microglobulin (b2-M) in patients with acute pulmonary embolism (PE). We conducted a prospective study of 109 patients admitted in a pulmonary clinic due to acute PE. A panel of inflammatory markers including b2-M white blood cell (WBC) count and C-reactive protein (CRP) was determined for each patient. In this preliminary study, baseline b2-M levels significantly correlated with the impairment of oxygenation and with all the parameters that are used for the early risk stratification of patients. In multivariate analysis, patients’ age and baseline b2-M levels were significantly associated with an increased risk of death. These findings require further prospective validation.


2006 ◽  
Vol 27 (2) ◽  
pp. 103-107 ◽  
Author(s):  
Timo A. Lakka ◽  
Tuomo Rankinen ◽  
Treva Rice ◽  
Arthur S. Leon ◽  
D. C. Rao ◽  
...  

C-reactive protein (CRP) is a sensitive marker of systemic low-grade inflammation. Increased plasma levels of CRP predict the risk of cardiovascular and metabolic diseases. Although genetic factors account for 30–40% of individual differences in plasma CRP levels, genomic regions contributing to CRP levels remain unknown. We performed a genome-wide linkage scan for plasma CRP levels in healthy whites from the HERITAGE Family Study. CRP was measured with a high-sensitivity assay. Multipoint linkage analyses were performed in 280 sibling pairs with 654 markers using regression and variance components-based methods. Data were adjusted for independent correlates of plasma CRP. We showed the strongest evidence of linkage for plasma CRP levels on chromosome 20q13. Markers which gave suggestive linkages in this region were D20S52 [logarithm of odds (LOD) score 3.18, P = 0.00006], D20S857 (LOD score 2.87, P = 0.00014), D20S869 (LOD score 2.75, P = 0.0002), D20S480 (LOD score 2.59, P = 0.0003), D20S501 (LOD score 2.55, P = 0.0003), D20S840 (LOD score 2.18, P = 0.0008), and D20S876 (LOD score 2.07, P = 0.001). We also detected suggestive linkage on chromosome 5p13 for marker D5S1470 (LOD score 2.23, P = 0.0007). Chromosome 20q13 may contribute to plasma CRP levels in healthy whites. This region contains genes that are important in the inflammatory process and may play a role in the development of chronic inflammatory diseases. The present findings may be useful in the ongoing effort to search for genes contributing to inflammation and to identify individuals at an increased risk of chronic inflammatory diseases.


2018 ◽  
Vol 19 (8) ◽  
pp. 2303 ◽  
Author(s):  
Frank You ◽  
Jin Xiao ◽  
Pingchuan Li ◽  
Zhen Yao ◽  
Gaofeng Jia ◽  
...  

A genome-wide association study (GWAS) was performed on a set of 260 lines which belong to three different bi-parental flax mapping populations. These lines were sequenced to an averaged genome coverage of 19× using the Illumina Hi-Seq platform. Phenotypic data for 11 seed yield and oil quality traits were collected in eight year/location environments. A total of 17,288 single nucleotide polymorphisms were identified, which explained more than 80% of the phenotypic variation for days to maturity (DTM), iodine value (IOD), palmitic (PAL), stearic, linoleic (LIO) and linolenic (LIN) acid contents. Twenty-three unique genomic regions associated with 33 quantitative trait loci (QTL) for the studied traits were detected, thereby validating four genomic regions previously identified. The 33 QTL explained 48–73% of the phenotypic variation for oil content, IOD, PAL, LIO and LIN but only 8–14% for plant height, DTM and seed yield. A genome-wide selective sweep scan for selection signatures detected 114 genomic regions that accounted for 7.82% of the flax pseudomolecule and overlapped with the 11 GWAS-detected genomic regions associated with 18 QTL for 11 traits. The results demonstrate the utility of GWAS combined with selection signatures for dissection of the genetic structure of traits and for pinpointing genomic regions for breeding improvement.


2019 ◽  
Vol 8 (1) ◽  
pp. 58-62
Author(s):  
Ram Sagar Shah ◽  
Kaushal Sigdel

Background: To determine the relationship between expulsion rate of distal ureteric calculus less than orequal to 10mm in size and C reactive protein (CRP) level, white cell count and neutrophil percentage. Materials and Methods: A total of 186 patients with distal ureteric calculus of ≤10mm were evaluated for stone expulsion rate and its correlation with serum CRP, white cell count and neutrophil percentage. All patients received tablet Tamsulosin 0.4mg for 4 weeks or till the expulsion of stone. Patients were called weekly till 4 weeks, or early if there was history of stone expulsion. Patients were divided in two groups according to normal and elevated CRP levels, white cell count and neutrophil percent age at baseline for statistical analysis. Results: The patients had an average age of 35.6 } 13.9 years. 52.2% were male. Ratio of right to left was1.58:1. Majority of the patients with distal ureteric calculus ≤ 10mm passed their stone (74.7 %) with medical expulsion therapy. Expulsion of stone less than 5mm was statistically significant (p0.017). Patients with normal neutrophil percentage and normal CRP level had higher stone expulsion rate than elevated neutrophil or CRP (85.2% vs. 40.9, 91.8% vs. 30.8% respectively).In patients with normal white cell count, 86.4% passed their stone while in elevated white cellcount group 39.1% passed their stone. Conclusion: This study showed patients with distal ureteric calculus of ≤10mmwith normal CRP level and normal neutrophil count had higher expulsion rate while WBC count showed no statistically significant association.


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