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• W2414231872 abstract "Objective: The genetic architecture of type 2 diabetes (T2D) has been reported to be different between Asian and Caucasian populations (BBRC 2014;452:213–220). It is also well recognized that renal complications of T2D start earlier and are more severe in Asian subjects. Our objective was to determine whether such heterogeneity exists within the Caucasian population with respect to phenotypic and genomic determinants of renal complications in T2D. Design and method: We analyzed two major aspects of renal impairment: increase of albuminuria as UACR and decline of estimated glomerular filtration rate as log(eGFR) in Caucasian patients during the 5 year period of the ADVANCE trial (NEJM 2014;371:1392–406). Celto-Germanic and Slavic origins of 3449 genotyped subjects were determined by principal component analysis with Eigenstrat software. The first principal component separated the 3449 individuals along a geographical gradient from East/West Europe: 1133 T2D patients were Slavic and 2316 were Celto-Germanic. Phenotypic analyses and Genome Wide Association Studies (GWAS) were performed in the two groups separately. Results: The prevalence of hypertension was significantly higher (p = 1.7x10–32) in ADVANCE Slavic subjects. The prevalence of albuminuria and UACR levels were significantly higher (p = 10–4 and 9.5x10–5, respectively) at baseline and its progression over the 5-year period was steeper (p = 6.2x10–4) in patients of Slavic origin, contrasting with a more significant decline of eGFR in Celto-Germanic subjects (p = 4.9x10–21). Other T2D outcomes (myocardial infarction and stroke) did not exhibit such a difference between East and West Europe. GWAS analyses of eGFR decline did not reveal any associated SNPs (threshold p-value of < 10–3) in common between the two geo-ethnic groups and only 6% of associated genes were shared. Similarly, GWAS of UACR progression showed that only 0.1% of SNPs were common and 7% of genes were shared between the two groups. This was very different for stroke: 25% of SNPs and more than 50% of genes were common. Conclusions: Genetic analyses have to consider geo-ethnic characteristics even within Caucasians, demonstrated here for cardinal features of renal impairment in T2D. Our data suggest that distinct understanding of genomic architectures is important to ascertain clinical utility." @default.
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• W2414231872 date "2015-06-01" @default.
• W2414231872 modified "2023-10-01" @default.
• W2414231872 title "1A.09" @default.
• W2414231872 doi "https://doi.org/10.1097/01.hjh.0000467359.89462.ce" @default.
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