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

@article{citeulike:1406126, abstract = {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 HbA(1c), 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.}, address = {Faculty of Medicine, Department of Pathophysiology, Masaryk University Brno, Komenskeho nam. 2, 662 43, Brno, Czech Republic, kankov@med.muni.cz.}, author = {Kankov\'{a}, K. and Stejskalov\'{a}, A. and P\'{a}cal, L. and Tschoplov\'{a}, S. and Hertlov\'{a}, M. and Krusov\'{a}, D. and Izakovicov\'{a}-Holl\'{a}, L. and Ber\'{a}nek, M. and Vask\r{u}, A. and Barral, S. and Ott, J. }, citeulike-article-id = {1406126}, doi = {10.1007/s00125-007-0606-3}, issn = {0012-186X}, journal = {Diabetologia}, keywords = {dn, genetics, snp}, month = {May}, number = {5}, pages = {990--999}, posted-at = {2007-06-23 08:32:50}, priority = {2}, title = {Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach.}, url = {http://dx.doi.org/10.1007/s00125-007-0606-3}, volume = {50}, year = {2007} }

TY - JOUR ID - citeulike:1406126 L3 - citeulike-article-id:1406126 TI - Genetic risk factors for diabetic nephropathy on chromosomes 6p and 7q identified by the set-association approach. JF - Diabetologia VL - 50 IS - 5 SP - 990 EP - 999 AD - Faculty of Medicine, Department of Pathophysiology, Masaryk University Brno, Komenskeho nam. 2, 662 43, Brno, Czech Republic, kankov@med.muni.cz. SN - 0012-186X N2 - 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 HbA(1c), 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. KW - dn KW - genetics KW - snp AU - Kanková, K AU - Stejskalová, A AU - Pácal, L AU - Tschoplová, S AU - Hertlová, M AU - Krusová, D AU - Izakovicová-Hollá, L AU - Beránek, M AU - Vasků, A AU - Barral, S AU - Ott, J PY - 2007/05// UR - http://dx.doi.org/10.1007/s00125-007-0606-3 ER -