title: Strong association of insulin gene INS-VNTR polymorphisms with type 1 diabetes in the Romanian population.
abstract: Type 1 diabetes (T1DM) is a common, chronic disease with autoimmune pathogeny, conditioned by genetic factors. Class II HLA DR and DQ and insulin gene polymorphisms encode for most of the T1DM genetic susceptibility. We have previously shown that class I alleles of the insulin gene INS-VNTR locus are strongly associated with T1DM in the Romanian population. The aim of our study was to confirm the contribution of INS-VNTR to T1DM genetic susceptibility in Romania. For this we typed the insulin gene -23HphI A/T polymorphism (an accurate marker for the INS-VNTR alleles) on 219 Romanian T1DM families using Taqman. Allele transmission to diabetics and unaffected siblings was assessed using the Transmission Disequilibrium Test (TDT). We found a significantly increased transmission of -23HphI A allele to diabetics (78.31% transmission, pTDT = 2.4 e-07) which confirms our previous findings. Combined with the data from the first 204 Romanian T1DM families, the transmission of -23HphI A allele to diabetics is almost 80% (79.78%, pTDT = 2.8 e-15). This percentage indicates the same level of predisposition as for the most diabetogenic HLA's. In conclusion, our results indicate an exceptionally strong association of the class I INS-VNTR alleles with T1DM for the Romanian population.
authors.affiliation: Clinic of Diabetes, Institute of Diabetes, Nutrition and Metabolic Diseases N. Paulescu, Bucharest, Romania. cristi_guja@fx.ro
authors.forename: C
authors.initials: C
authors.lastname: Guja
authors.forename: Loreta
authors.initials: L
authors.lastname: Guja
authors.forename: Sarah
authors.initials: S
authors.lastname: Nutland
authors.forename: Helen
authors.initials: H
authors.lastname: Rance
authors.forename: J A
authors.initials: JA
authors.lastname: Todd
authors.forename: C
authors.initials: C
authors.lastname: Ionescu-Tîrgovişte
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007223:Infant; D008297:Male; D018598:Minisatellite Repeats; D020641:Polymorphism, Single Nucleotide; D012383:Romania / Q000453:epidemiology