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Gene-Gene Associations with the Susceptibility of Kawasaki Disease and Coronary Artery Lesions.

Kuo HC, Chang JC, Guo MM, Hsieh KS, Yeter D, Li SC, Yang KD - PLoS ONE (2015)

Bottom Line: We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models.UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05).Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

ABSTRACT
Kawasaki disease (KD) is a systemic vasculitis primarily affecting children < 5 years old. Genes significantly associated with KD mostly involve cardiovascular, immune, and inflammatory responses. Recent studies have observed stronger associations for KD risk with multiple genes compared to individual genes. Therefore, we investigated whether gene combinations influenced KD susceptibility or coronary artery lesion (CAL) formation. We examined 384 single-nucleotide polymorphisms (SNPs) for 159 immune-related candidate genes in DNA samples from KD patients with CAL (n = 73), KD patients without CAL (n = 153), and cohort controls (n = 575). Individual SNPs were first assessed by univariate analysis (UVA) and multivariate analysis (MVA). We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models. UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05). Significant associations in MDR analysis were only observed for the two-locus models after permutation testing (p ≤ 0.05). In logistic regression, combined possession of PDE2A (rs341058) and CYFIP2 (rs767007) significantly increased KD susceptibility (OR = 3.54; p = 4.14 x 10(-7)), while combinations of LOC100133214 (rs2517892) and IL2RA (rs3118470) significantly increased the risk of CAL in KD patients (OR = 5.35; p = 7.46 x 10(-5)). Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.

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LOC100133214 (rs2517892) and IL2RA (rs3118470) gene-gene interaction in a 2-way mode of MDR analysis.The interaction of LOC100133214 and IL2RA was significantly associated with a higher risk of CAL formation using logistic regression of our MDR results from KD patients with CAL (n = 73) and KD patients without CAL (n = 153), with an odds ratio of 5.35 (95% CI: 2.33–12.25) and a p-value of 7.46 x 10−5. (A) MDR classified the nine interactive items into high- or low-risk CAL groups, which were significantly different in our further analysis using the Chi-square test (p = 3.36 x 10−6). (B).
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pone.0143056.g002: LOC100133214 (rs2517892) and IL2RA (rs3118470) gene-gene interaction in a 2-way mode of MDR analysis.The interaction of LOC100133214 and IL2RA was significantly associated with a higher risk of CAL formation using logistic regression of our MDR results from KD patients with CAL (n = 73) and KD patients without CAL (n = 153), with an odds ratio of 5.35 (95% CI: 2.33–12.25) and a p-value of 7.46 x 10−5. (A) MDR classified the nine interactive items into high- or low-risk CAL groups, which were significantly different in our further analysis using the Chi-square test (p = 3.36 x 10−6). (B).

Mentions: The MDR results of these significant associations in the two-locus model were further analyzed using the Chi-square test. As shown in Fig 1A and 1B, our classification of varying allele combinations for the PDE2A and CYFIP2 SNPs identified in MDR revealed four low-risk genotypes (n = 358) and five high-risk genotypes (n = 443) that significantly differed between the KD group and cohort controls (p = 9.71 x 10−7). As shown in Fig 2A and 2B, our classification of varying allele combinations for the LOC100133214 and IL2RA SNPs revealed four low-risk genotypes (n = 118) and five high-risk genotypes (n = 108) that differed significantly between KD patients with subsequent CAL formation and KD patients without CAL (p = 3.36 x 10−6).


Gene-Gene Associations with the Susceptibility of Kawasaki Disease and Coronary Artery Lesions.

Kuo HC, Chang JC, Guo MM, Hsieh KS, Yeter D, Li SC, Yang KD - PLoS ONE (2015)

LOC100133214 (rs2517892) and IL2RA (rs3118470) gene-gene interaction in a 2-way mode of MDR analysis.The interaction of LOC100133214 and IL2RA was significantly associated with a higher risk of CAL formation using logistic regression of our MDR results from KD patients with CAL (n = 73) and KD patients without CAL (n = 153), with an odds ratio of 5.35 (95% CI: 2.33–12.25) and a p-value of 7.46 x 10−5. (A) MDR classified the nine interactive items into high- or low-risk CAL groups, which were significantly different in our further analysis using the Chi-square test (p = 3.36 x 10−6). (B).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4664466&req=5

pone.0143056.g002: LOC100133214 (rs2517892) and IL2RA (rs3118470) gene-gene interaction in a 2-way mode of MDR analysis.The interaction of LOC100133214 and IL2RA was significantly associated with a higher risk of CAL formation using logistic regression of our MDR results from KD patients with CAL (n = 73) and KD patients without CAL (n = 153), with an odds ratio of 5.35 (95% CI: 2.33–12.25) and a p-value of 7.46 x 10−5. (A) MDR classified the nine interactive items into high- or low-risk CAL groups, which were significantly different in our further analysis using the Chi-square test (p = 3.36 x 10−6). (B).
Mentions: The MDR results of these significant associations in the two-locus model were further analyzed using the Chi-square test. As shown in Fig 1A and 1B, our classification of varying allele combinations for the PDE2A and CYFIP2 SNPs identified in MDR revealed four low-risk genotypes (n = 358) and five high-risk genotypes (n = 443) that significantly differed between the KD group and cohort controls (p = 9.71 x 10−7). As shown in Fig 2A and 2B, our classification of varying allele combinations for the LOC100133214 and IL2RA SNPs revealed four low-risk genotypes (n = 118) and five high-risk genotypes (n = 108) that differed significantly between KD patients with subsequent CAL formation and KD patients without CAL (p = 3.36 x 10−6).

Bottom Line: We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models.UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05).Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.

View Article: PubMed Central - PubMed

Affiliation: Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.

ABSTRACT
Kawasaki disease (KD) is a systemic vasculitis primarily affecting children < 5 years old. Genes significantly associated with KD mostly involve cardiovascular, immune, and inflammatory responses. Recent studies have observed stronger associations for KD risk with multiple genes compared to individual genes. Therefore, we investigated whether gene combinations influenced KD susceptibility or coronary artery lesion (CAL) formation. We examined 384 single-nucleotide polymorphisms (SNPs) for 159 immune-related candidate genes in DNA samples from KD patients with CAL (n = 73), KD patients without CAL (n = 153), and cohort controls (n = 575). Individual SNPs were first assessed by univariate analysis (UVA) and multivariate analysis (MVA). We used multifactor dimensionality reduction (MDR) to examine individual SNPs in one-, two-, and three-locus best fit models. UVA identified 53 individual SNPs that were significantly associated with KD risk or CAL formation (p < 0.10), while 35 individual SNPs were significantly associated using MVA (p ≤ 0.05). Significant associations in MDR analysis were only observed for the two-locus models after permutation testing (p ≤ 0.05). In logistic regression, combined possession of PDE2A (rs341058) and CYFIP2 (rs767007) significantly increased KD susceptibility (OR = 3.54; p = 4.14 x 10(-7)), while combinations of LOC100133214 (rs2517892) and IL2RA (rs3118470) significantly increased the risk of CAL in KD patients (OR = 5.35; p = 7.46 x 10(-5)). Our results suggest varying gene-gene associations respectively predispose individuals to KD risk or its complications of CAL.

Show MeSH
Related in: MedlinePlus