Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach.

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Research Abstract Details 

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Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Abstract Text:

K ,A ,L ,S ,M ,D ,L ,M ,A Vask?,S Barral,J Ott,

AIMS/HYPOTHESIS: In the present study we investigated potential associations of a set of 45 single nucleotide polymorphisms (SNP) in 20 candidate genes on eight chromosomes with diabetic nephropathy (DN) in type 2 diabetes mellitus. We aimed to compare two methodological approaches suitable for analysing susceptibility to complex traits: single- and multi-locus analyses. MATERIALS AND METHODS: The study comprised a total of 647 subjects in one of three groups: diabetes with or without DN, or no diabetes. Genotypes were detected by PCR-based methodology (PCR only, PCR plus RFLP, or allele-specific PCR). Haplotypes were inferred in silico. Set association (tested using SUMSTAT software) was used for multilocus analysis. RESULTS: After correction for multiple comparisons, only one SNP, in the gene encoding the receptor of advanced glycation end products, AGER 2184A/G (gene symbol formerly known as RAGE) showed a significant association with DN (p = 0.0006) in single-locus analysis. In multi-locus analysis, six SNPs exhibited a significant association with DN: four SNPs on chromosome 6p (AGER 2184A/G, LTA 252A/G, EDN1 8002G/A and AGER -429T/C) and two SNPs on chromosome 7q (NOS3 774C/T and NOS3 E298D), omnibus p = 0.033. Haplotype analysis revealed significant differences between DN and control groups in haplotype frequencies on chromosome 6 (p = 0.0002); however, there were no significant difference in the frequencies of the NOS3 haplotypes on chromosome 7. Logistic regression analysis identified SNPs AGER 2184A/G and NOS3 774C/T, together with diabetes duration and HbA1c, as significant predictors of DN. Testing for interactions between SNPs on chromosomes 6 and 7 did not provide significant evidence for epistatic interaction. CONCLUSIONS/INTERPRETATION: Using the set-association approach we identified significant associations of several SNPs on chromosomes 6 and 7 with DN. The single- and multi-locus analyses represent complementary methods.

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Publishing Authors By Initials

K ,A ,L ,S ,M ,D ,L ,M ,A Vask?,S Barral,J Ott,

For similar investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research

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Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Diabetologia

VOLUME: 50

Page Numbers: 990-9

Journal Abbreviation:

ISSN: 0012-186X

DAY: 8

MONTH: 03

YEAR: 2007

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Information

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LANGUAGE: eng

NlmUniqueID: 6777

Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. Keywords Mesh Terms:

KEYWORDS: Risk Factors

MESH TERMS: genetics

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Grant and Affiliation Information for Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach.

AFFILIATION: Faculty of Medicine, Department of Pathophysiology, Masaryk University Brno, Komenskeho nam. 2, 662 43 Brno, Czech Republic. kankov@med.muni.cz

Country: Germany

AGENCY: United States NIMH

GRANT: MH44292

ACRONYM: MH

MEDLINETA: Diabetologia

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