Polymorphisms in the RAGE gene influence susceptibility to diabetes-associated microvascular dermatoses in NIDDM.
To examine genetic polymorphism in the complete sequence of the Receptor of Advanced Glycation End products (RAGE) gene and its possible associations with diabetes-associated microvascular dermatoses (DAMD). Further, to analyze the distribution of individual genotype combinations on the particular polymorphic loci in the RAGE gene. A part of the RAGE gene spanning a region from -4 to 3334 bp was analyzed on a set of 45 subjects with non-insulin dependent diabetes mellitus (NIDDM) and parallel DAMD by means of PCR with subsequent heteroduplex and single-strand conformation polymorphism (SSCP) analyses. Allele frequencies and genotype combinations of novel common polymorphisms were determined in an associations study comprising four groups of subjects (n=390). Fourteen novel polymorphisms (R77C, V89V, 718G/T, 1704G/T, 1727A1728ins, H305Q, S307C, 2117A/G, 2184A/G, 2245G/A, 2249A/G, 2741G/A, and 3089ACdel) and one described previously (G82S) were identified. Significant association with microvascular dermatoses (MD) irrespective of NIDDM were found for exon mutation 82S (P= .004, after a correction for the number of comparisons P(corr) < .05) and marginally significant for intron variant 1704T (P= .032, P(corr)> .05). Calculated odds ratios for 82S and 1704T were 4.73 (95% CI, 1.51 to 14.77) and 1.73 (95% CI, 0.93 to 3.22), respectively. Certain individual genotype combinations of G82S, 1704G/T, and 2184A/G were significantly associated with the presence of MD (P= .00647) both in diabetic and non-diabetic study populations. The two novel polymorphisms (1704G/T and 2184A/G) together with the G82S were shown to influence the susceptibility to MD independent of diabetes itself.
Kanková
K
K
Department of Pathophysiology, Faculty of Medicine, Masaryk University, Komenského nám. 2, 662 43 Brno, Czech Republic. kankov@med.muni.cz
Záhejský
J
J
Márová
I
I
Muzík
J
J
Kuhrová
V
V
Blazková
M
M
Znojil
V
V
Beránek
M
M
Vácha
J
J
D000368:Aged; D019943:Amino Acid Substitution; D018153:Czech Republic; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000235:genetics* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000235:genetics*; D005091:Exons; D005260:Female; D020022:Genetic Predisposition to Disease; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006801:Humans; D008297:Male; D008833:Microcirculation / Q000503:physiopathology*; D008875:Middle Aged; D020125:Mutation, Missense; D017354:Point Mutation; D011110:Polymorphism, Genetic; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D012867:Skin / Q000098:blood supply; D012871:Skin Diseases / Q000150:complications / Q000235:genetics*; D044465:White People
D017127:Glycation End Products, Advanced; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic