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http://purl.uniprot.org/citations/31733101http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
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Background

Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthases, making it a contributing factor for diabetes. Endogenous ADMA is hydrolyzed by dimethylarginine dimethylaminohydrolase 1 (DDAH1), and a DDAH1 promoter -396 4N deletion/insertion polymorphism (DDAH1: -396_-395insGCGT) regulates its transcriptional activity. This study aimed to explore the association between this polymorphism and type 2 diabetes (T2DM).

Methods

In a case-control study, all participants were genotyped for this polymorphism within two sets of populations (discovery: 1,227 T2DM patients and 1,339 controls; replication: 1,190 patients and 1,651 controls). The disease association was assessed by a unconditional logistic regression model. Homeostasis model assessment calculations were conducted among different genotypes.

Results

We identified that DDAH1: -396_-395insGCGT insertion allele was significantly associated with increased risk of T2DM (discovery: adjusted odds ratio [OR] = 1.380, 95% CI = 1.128-1.687, p = .002; replication: OR = 1.231, 95% CI = 1.007-1.504, p = .043). The homeostasis model assessment of insulin resistance was increased in participants carrying Ins/Ins alleles (p = .0452). Interestingly, the insertion allele increased the risk of T2DM in males but not in females (male discovery: OR = 1.528, 95% CI = 1.141-2.047, p = .004; replication: OR = 1.439, 95% CI = 1.083-1.911, p = .012; female discovery: OR = 1.218, 95% CI = 0.913-1.626, p = .18; replication: OR = 1.161, 95% CI = 0.871-1.548, p = .308).

Conclusion

The DDAH1: -396_-395insGCGT insertion allele is associated with increased risk of T2DM in a gender-dependent manner, affects males but not females."xsd:string
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http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/author"Zhou C."xsd:string
http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/author"Zhu F."xsd:string
http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/author"Wen Z."xsd:string
http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/author"Wang D.W."xsd:string
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http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/name"Mol Genet Genomic Med"xsd:string
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http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/title"DDAH1 promoter -396 4N insertion variant is associated with increased risk of type 2 diabetes in a gender-dependent manner."xsd:string
http://purl.uniprot.org/citations/31733101http://purl.uniprot.org/core/volume"8"xsd:string
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