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Polymorphisms of the CD24 Gene Are Associated with Risk of Multiple Sclerosis: A Meta-Analysis.

Braliou GG, Pantavou KG, Kontou PI, Bagos PG - Int J Mol Sci (2015)

Bottom Line: We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81).Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS.We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527-1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia 35100, Greece. gbraliou@dib.uth.gr.

ABSTRACT
CD24 is a cell-surface protein mainly expressed in cells of the immune and central nervous system (CNS), cells that play a critical role in the development of multiple sclerosis (MS). In the current study, we investigated four polymorphisms of the CD24 gene regarding their associations with MS. To this end, univariate and multivariate meta-analysis were applied along with modifications to include data from family-trios so as to increase the robustness of the meta-analysis. We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81). Moreover, the 1527-1528 TG>del polymorphism is inversely associated with MS according to the dominant mode of inheritance (odds ratio = 0.57; 95% CI 0.39, 0.83). Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS. We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527-1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.

No MeSH data available.


Related in: MedlinePlus

Forest plot of the meta-analysis for the association of the 226 C>T (Ala57Val) polymorphism of the CD24 gene with multiple sclerosis. For each study the estimate of the variance, OR and its respective 95% Confidence Interval (CI) are plotted with a box and a horizontal line, respectively. The dashed vertical lines indicate the overall estimate, whereas the solid ones indicate the  effect (OR = 1). The ORs correspond to (A) the allele contrast T vs. C; (B) the TT vs. TC + CC contrast and (C) the TT + TC vs. CC genotype contrast.
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ijms-16-12368-f001: Forest plot of the meta-analysis for the association of the 226 C>T (Ala57Val) polymorphism of the CD24 gene with multiple sclerosis. For each study the estimate of the variance, OR and its respective 95% Confidence Interval (CI) are plotted with a box and a horizontal line, respectively. The dashed vertical lines indicate the overall estimate, whereas the solid ones indicate the effect (OR = 1). The ORs correspond to (A) the allele contrast T vs. C; (B) the TT vs. TC + CC contrast and (C) the TT + TC vs. CC genotype contrast.

Mentions: The results of the eight populations analyzed in the present meta-analysis [11,18,19,20,21,22,23] suggested an association of the 226 C>T polymorphism with MS. The T vs. C contrast (incorporating data from family trios) produced a significant association with OR 1.26 and 95% CI: 1.02–1.56. Similarly, both recessive and dominant modes resulted in significant association (OR 1.75, 95% CI: 1.09–2.81 for TT vs. TC + CC and 1.36, 95% CI: 1.14–1.63 for TT + TC vs. CC) (Figure 1A–C). When the above contrasts were performed only with populations obeying Hardy Weinberg Equilibrium (HWE) the association remained significant (Table 3). Because two studies included data only for combined genotypes, only six studies were employed in the TT + TC vs. CC contrast. The allele and recessive contrasts presented higher heterogeneity compared to the dominant mode (Table 3). Time-trend and Proteus phenomenon were not detected in the cumulative meta-analysis for all contrasts. Sensitivity analysis (i.e., removing a study and performing the meta-analysis again) showed that five out of the eight studies were necessary for achieving statistical significance, a finding that was expected considering the fact that the lower limit of the 95% confidence interval of the pooled estimate was close to unity. Nevertheless, the magnitude of the pooled OR did not change significantly in the sensitivity analysis (data not shown).


Polymorphisms of the CD24 Gene Are Associated with Risk of Multiple Sclerosis: A Meta-Analysis.

Braliou GG, Pantavou KG, Kontou PI, Bagos PG - Int J Mol Sci (2015)

Forest plot of the meta-analysis for the association of the 226 C>T (Ala57Val) polymorphism of the CD24 gene with multiple sclerosis. For each study the estimate of the variance, OR and its respective 95% Confidence Interval (CI) are plotted with a box and a horizontal line, respectively. The dashed vertical lines indicate the overall estimate, whereas the solid ones indicate the  effect (OR = 1). The ORs correspond to (A) the allele contrast T vs. C; (B) the TT vs. TC + CC contrast and (C) the TT + TC vs. CC genotype contrast.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490449&req=5

ijms-16-12368-f001: Forest plot of the meta-analysis for the association of the 226 C>T (Ala57Val) polymorphism of the CD24 gene with multiple sclerosis. For each study the estimate of the variance, OR and its respective 95% Confidence Interval (CI) are plotted with a box and a horizontal line, respectively. The dashed vertical lines indicate the overall estimate, whereas the solid ones indicate the effect (OR = 1). The ORs correspond to (A) the allele contrast T vs. C; (B) the TT vs. TC + CC contrast and (C) the TT + TC vs. CC genotype contrast.
Mentions: The results of the eight populations analyzed in the present meta-analysis [11,18,19,20,21,22,23] suggested an association of the 226 C>T polymorphism with MS. The T vs. C contrast (incorporating data from family trios) produced a significant association with OR 1.26 and 95% CI: 1.02–1.56. Similarly, both recessive and dominant modes resulted in significant association (OR 1.75, 95% CI: 1.09–2.81 for TT vs. TC + CC and 1.36, 95% CI: 1.14–1.63 for TT + TC vs. CC) (Figure 1A–C). When the above contrasts were performed only with populations obeying Hardy Weinberg Equilibrium (HWE) the association remained significant (Table 3). Because two studies included data only for combined genotypes, only six studies were employed in the TT + TC vs. CC contrast. The allele and recessive contrasts presented higher heterogeneity compared to the dominant mode (Table 3). Time-trend and Proteus phenomenon were not detected in the cumulative meta-analysis for all contrasts. Sensitivity analysis (i.e., removing a study and performing the meta-analysis again) showed that five out of the eight studies were necessary for achieving statistical significance, a finding that was expected considering the fact that the lower limit of the 95% confidence interval of the pooled estimate was close to unity. Nevertheless, the magnitude of the pooled OR did not change significantly in the sensitivity analysis (data not shown).

Bottom Line: We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81).Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS.We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527-1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.

View Article: PubMed Central - PubMed

Affiliation: Department of Computer Science and Biomedical Informatics, University of Thessaly, Lamia 35100, Greece. gbraliou@dib.uth.gr.

ABSTRACT
CD24 is a cell-surface protein mainly expressed in cells of the immune and central nervous system (CNS), cells that play a critical role in the development of multiple sclerosis (MS). In the current study, we investigated four polymorphisms of the CD24 gene regarding their associations with MS. To this end, univariate and multivariate meta-analysis were applied along with modifications to include data from family-trios so as to increase the robustness of the meta-analysis. We found that the polymorphism 226 C>T (Ala57Val) of the CD24 gene is associated with MS according to the recessive mode of inheritance (odds ratio = 1.75; 95% CI: 1.09, 2.81). Moreover, the 1527-1528 TG>del polymorphism is inversely associated with MS according to the dominant mode of inheritance (odds ratio = 0.57; 95% CI 0.39, 0.83). Conversely, the 1056 A>G and 1626 A>G polymorphisms were not found to be associated with MS. We conclude that the CD24 226 C>T polymorphism increases the risk of MS, while the 1527-1528 TG>del polymorphism seems to have a protective role against MS, suggesting that these two polymorphisms can be used as predictive biomarkers for MS development.

No MeSH data available.


Related in: MedlinePlus