Lack of evidence for association of two functional SNPs of CHI3L1 gene (HC-gp39) with rheumatoid arthritis

Srivastava, Sanjeev K.; Antal, Péter; Gál, János; Hullám, Gábor; Semsei, Ágnes F.; Nagy, György; Falus, András; Buzás, Edit I.

doi:10.1007/s00296-010-1396-3

Cited by 9 publications

(8 citation statements)

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“…SEMA3G is another potential marker for adipogenesis, has an inhibitory effect on tumor progression [57], and takes part in controlling the function of endothelial cells and smooth muscle cells [58]. CHI3L1 encodes a glycoprotein that takes part in macrophage differentiation [59] and has an association with chondrocytes but no association with rheumatoid arthritis [60]. RARRES1 is a retinoic acid receptor that acts as a vital tumor suppressor gene [61].…”

Section: Discussionmentioning

confidence: 99%

Reverse Differentiation as a Gene Filtering Tool in Genome Expression Profiling of Adipogenesis for Fat Marker Gene Selection and Their Analysis

et al. 2013

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BackgroundDuring mesenchymal stem cell (MSC) conversion into adipocytes, the adipogenic cocktail consisting of insulin, dexamethasone, indomethacin and 3-isobutyl-1-methylxanthine not only induces adipogenic-specific but also genes for non-adipogenic processes. Therefore, not all significantly expressed genes represent adipogenic-specific marker genes. So, our aim was to filter only adipogenic-specific out of all expressed genes. We hypothesize that exclusively adipogenic-specific genes change their expression during adipogenesis, and reverse during dedifferentiation. Thus, MSC were adipogenic differentiated and dedifferentiated.ResultsAdipogenesis and reverse adipogenesis was verified by Oil Red O staining and expression of PPARG and FABP4. Based on GeneChips, 991 genes were differentially expressed during adipogenesis and grouped in 4 clusters. According to bioinformatic analysis the relevance of genes with adipogenic-linked biological annotations, expression sites, molecular functions, signaling pathways and transcription factor binding sites was high in cluster 1, including all prominent adipogenic genes like ADIPOQ, C/EBPA, LPL, PPARG and FABP4, moderate in clusters 2–3, and negligible in cluster 4. During reversed adipogenesis, only 782 expressed genes (clusters 1–3) were reverted, including 597 genes not reported for adipogenesis before. We identified APCDD1, CHI3L1, RARRES1 and SEMA3G as potential adipogenic-specific genes.ConclusionThe model system of adipogenesis linked to reverse adipogenesis allowed the filtration of 782 adipogenic-specific genes out of total 991 significantly expressed genes. Database analysis of adipogenic-specific biological annotations, transcription factors and signaling pathways further validated and valued our concept, because most of the filtered 782 genes showed affiliation to adipogenesis. Based on this approach, the selected and filtered genes would be potentially important for characterization of adipogenesis and monitoring of clinical translation for soft-tissue regeneration. Moreover, we report 4 new marker genes.

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Section: Discussionmentioning

confidence: 99%

Reverse Differentiation as a Gene Filtering Tool in Genome Expression Profiling of Adipogenesis for Fat Marker Gene Selection and Their Analysis

et al. 2013

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“…We focused on the g.-131(C > G) allele and closely related polymorphisms described in Caucasian populations [26,36-39,43,44,46]. The g.1219(G > A) polymorphism was also included as one study reported an individual functional property of this polymorphism [43].…”

Section: Discussionmentioning

confidence: 99%

“…Only one small study has evaluated CHI3L1 polymorphisms in patients with RA [46]. In 182 Hungarian patients with RA and 194 healthy controls there were no significant differences in genotype frequencies for the g.-131(C > G) or the g.-329(C > T) polymorphisms between the two groups.…”

Section: Introductionmentioning

confidence: 99%

Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects

et al. 2011

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IntroductionThe present study investigates the association between single nucleotide polymorphisms (SNPs) in the chitinase 3-like 1 (CHI3L1) gene and serum concentrations of YKL-40 in Danish patients with rheumatoid arthritis (RA) and healthy controls as well as the association with RA in the Danish population. The CHI3L1 gene is located on chromosome 1q32.1 and encodes the YKL-40 glycoprotein. YKL-40 concentrations are elevated in the serum of patients with RA compared to healthy subjects, and YKL-40 has been suggested to be an auto-antigen and may play a role in development of RA and in inflammation.MethodsEight SNPs in the CHI3L1 gene and promotor were genotyped in 308 patients with RA and 605 controls (healthy blood donors) using TaqMan allele discrimination assays. Serum concentrations of YKL-40 were determined by an enzyme-linked immunosorbent assay (ELISA).ResultsWe found significant association between the serum concentrations of YKL-40 and polymorphism in the CHI3L1 gene among both patients with RA and controls. The g.-131(C > G) polymorphism (rs4950928) was most strongly associated with age adjusted serum concentrations of YKL-40 in patients with RA (P < 2.4e-8) and controls (P < 2.2e-16). No significant allelic- or genotypic association with RA was found in this Danish cohort.ConclusionsWe suggest that the g.-131(C > G) promoter polymorphism has a substantial impact on serum concentrations of YKL-40 in patients with RA and healthy subjects. However, the polymorphism does not seem to confer risk to RA itself. The effect of CHI3L1 polymorphism on clinical outcome or the response to treatment in patients with RA remains to be investigated.

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“…Interestingly, no significant association of rs4950928 C>G was observed with the susceptibility to several diseases, such as colorectal cancer [35] and peripheral artery disease [36]. Also, rs10399931 C>T has also been shown to have no relations with coronary heart disease [37], coronary artery disease [38] and rheumatoid arthritis [39]. The reason for the above inconsistency was likely that the two SNPs of this gene might have different functions in different types of diseases.…”

Section: Discussionmentioning

confidence: 90%

Association of the Polymorphisms and Plasma Level of CHI3L1 with Alzheimer’s Disease in the Chinese Han Population: A Case-Control Study

Dai¹,

Gong²

2018

Neuropsychobiology

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Objective: To investigate whether the polymorphisms and plasma level of chitinase-3-like protein 1 (CHI3L1) are associated with Alzheimer’s disease (AD) in the Chinese Han population. Methods: A total of 166 patients who were initially diagnosed with AD were enrolled as the case group, and 184 healthy subjects were recruited as the healthy controls. TaqMan® SNP genotyping assays were applied for the genotyping of rs4950928, rs10399931 and rs6691378. The plasma level of CHI3L1 was determined by enzyme-linked immunosorbent assay. Results: The CG+GG genotype of rs4950928 C>G is a protective factor for AD and could effectively reduce the severity of AD. Patients with the CT+TT genotype of rs10399931 C>T had a significantly increased risk of AD, and it apparently aggravated the severity of AD. Moreover, the plasma CHI3L1 level in AD patients was significantly higher than that in healthy controls, which was increased with the severity of AD. A Kaplan-Meier survival curve showed that significant differences in 5-year survival rates were found in AD patients in different genotypes of CHI3L1 rs4950928 C>G and rs10399931 C>T. The AD patients and healthy controls who carried the CG+GG genotype of rs4950928 C>G had lower plasma CHI3L1 levels than CC genotype carriers. However, the CT+TT genotype of rs10399931 in the AD patients had an elevated plasma level of CHI3L1 as compared with the CC genotype. Binary logistic regression analysis showed that the plasma level of CHI3L1, the CC genotype of rs4950928 C>G and the CT+TT genotype of rs10399931 C>T were risk factors for AD. Conclusion: Polymorphisms of the CHI3L1 gene (rs4950928 C>G and rs10399931 C>T) are associated with the risk and prognosis of AD and can affect the expression of CHI3L1 in plasma.

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Lack of evidence for association of two functional SNPs of CHI3L1 gene (HC-gp39) with rheumatoid arthritis

Cited by 9 publications

References 29 publications

Reverse Differentiation as a Gene Filtering Tool in Genome Expression Profiling of Adipogenesis for Fat Marker Gene Selection and Their Analysis

Reverse Differentiation as a Gene Filtering Tool in Genome Expression Profiling of Adipogenesis for Fat Marker Gene Selection and Their Analysis

Promoter polymorphisms in the chitinase 3-like 1 gene influence the serum concentration of YKL-40 in Danish patients with rheumatoid arthritis and in healthy subjects

Association of the Polymorphisms and Plasma Level of CHI3L1 with Alzheimer’s Disease in the Chinese Han Population: A Case-Control Study

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