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Han male population GLUT9 gene promoter region of gout and hyperuricemia associated SNP loci screening

Author: ChuZuo
Tutor: LiChangGui
School: Qingdao University
Course: Endocrine and metabolic diseases
Keywords: SLC2A9 Gout hyperuricemia polymorphism Chinese
CLC: R589.7
Type: Master's thesis
Year: 2011
Downloads: 60
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Abstract


Objective:To investigate associations between gout and hyperuricemia and polymorphisms in the presumptive promoter region of GLUT9 in Chinese males.Methods:The approximately 2000bp presumptive promoter region upstream of the start site of exon 1 of GLUT9 was analyzed by direct sequencing and subjected to genetic analysis. A genotype-phenotype correlation was performed and polymorphisms-induced changes in transcription factor binding sites were predicted.Results:①Of 21 SNPs identified in GLUT9, five had not been previously reported.②Two of the SNPs (rs13124007 and rs6850166) were associated with susceptibility to gout (p=0.009 and p=0.042, respectively). The C allele of rs13124007 appeared to be the risk allele for predisposition to gout (p=0.006, OR 1.709 [95% CI 1.162-2.514]). For rs6850166, an increased risk of gout was associated with the A allele (p=0.029, OR 1.645 [95% CI 1.050-2.577]). Haplotype analyses showed that haplotype GG was a protective haplotype (p=0.0053) and haplotype CA was associated with increased risk of gout (p=0.0326).The C allele of rs13124007 (p=0.002, OR 2.191 [95% CI 1.305-3.679]) and the A allele of rs6850166 (p=0.046, OR 1.864 [95% CI 1.002-3.466]) might also be risk factors of tophus occurrence. Genotype-phenotype analysis among gout patients revealed an association of rs13124007 with serum triglycerides levels (P=0.001). The C to G substitution in polymorphism rs13124007 resulted in a loss of a binding site for transcription factor IRF-1.③Two (rs78201117and rs13137343) were associated with hyperuricemia (P=0.007 and P=0.045, respectively). The A allele of rs78201117 correlated with an increased risk of hyperuricemia (P=0.0078, OR 2.893 [95% CI 1.278-6.549]). Haplotype analyses indicated that the AT SNP was the risk haplotype (P= 0.0062, OR 6.265 [95% CI=1.396-28.113]). The G/A SNP in rs78201117 resulted in loss of a binding site for the transcription factors CCAAT/enhancer binding proteins delta (C/EBP delta) and Dl, and created a new site for transcription factor hemoglobin (Hb) and specificity protein 1 (Sp1). The T/G substitution in rs13137343 caused a loss of a binding site for neurofibromatosis-1 (NF-1) and the creation of a new binding site for the transcription factor CCAAT/enhancer binding proteins alpha (C/EBP alpha).Conclusion:Polymorphisms rs13124007 and rs6850166 are associated with susceptibility to gout and polymorphisms rs78201117and rs13137343 are associated with hyperuricemia in Chinese males.

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CLC: > Medicine, health > Internal Medicine > Endocrine diseases and metabolic diseases > Metabolic diseases > Metabolic disorder of purine ( Purine )
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