DIABETES/METABOLISM RESEARCH AND REVIEWS RESEARCH ARTICLE Diabetes Metab Res Rev 2010; 26: 474–480. Published online 6 July 2010 in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/dmrr.1103 The association of variable number of tandem repeats of the insulin gene with susceptibility to type 1 diabetes among Korean subjects Hye Rim Chung 1 Sei Won Yang 2 * Choong Ho Shin 2 Kyong Soo Park 3 Young Ah Lee 2 Jae Hyun Kim 4 Sun Hee Lee 5 Ji Hyun Kim 6 1 Department of Pediatrics, Seoul National University Bundang Hospital, Seongnam, Republic of Korea 2 Department of Pediatrics, Seoul National University Children’s Hospital, Seoul, Republic of Korea 3 Department of Internal Medicine, Seoul National University Hospital, Seoul, Republic of Korea 4 Department of Pediatrics, Inje University Ilsan Paik Hospital, Goyang, Republic of Korea 5 Department of Pediatrics, Inje University Pusan Paik Hospital, Pusan, Republic of Korea 6 Department of Pediatrics, Pohang St Mary’s Hospital, Pohang, Republic of Korea *Correspondence to: Sei Won Yang, Department of Pediatrics, Seoul National University Children’s Hospital, 28 Yeongeondong, Jongnogu, Seoul 110-744, Republic of Korea. E-mail: growth@snu.ac.kr Received: 15 December 2009 Revised: 29 May 2010 Accepted: 31 May 2010 Abstract Background There is ethnic variation in the variable number of tandem repeats of the insulin gene (INS VNTR), one of the susceptibility loci for developing type 1 diabetes (T1D). We evaluated the influence of the genotypes and subdivisions of INS VNTR on the development of T1D in Korean subjects. Methods The study included 352 Korean patients, under the age of 18 years who were diagnosed as having T1D, and 356 control subjects. The insulin −23HphI A/T single nucleotide polymorphism was used as a marker of class I and III alleles. Surrounding polymorphisms at nucleotide positions +1127, +1140, +2331 and +2336 were determined as subdivisions of INS VNTR. Results Classes I/I, I/III and III/III were observed at frequencies of 95.8, 4.2 and 0% among all subjects, respectively. Class I/III genotype was significantly less frequent in patients with T1D than in controls (2.56 versus 5.90%; odds ratio 0.419; P = 0.039). In a subdivision analysis, the ID/ID genotype was decreased among patients (P = 0.017, adjusted P = 0.085) and the IC allele tended to increase. The frequency of the class I/III genotype was significantly lower among patients who were diagnosed when younger than 7 years of age than in controls (odds ratio 0.115; P = 0.011). Conclusions INS VNTR has predominance of class I over class III alleles and is associated with susceptibility to T1D in Koreans. In addition, INS VNTR shows distinctive susceptibility according to the age at the onset of T1D. Copyright  2010 John Wiley & Sons, Ltd. Keywords type 1 diabetes; INS VNTR; susceptibility; Korean Introduction Type 1 diabetes (T1D) mellitus is caused by cell-mediated autoimmune destruction of pancreatic β cells. Both genetic and environmental factors are responsible for its pathogenesis [1,2]. Several chromosomal regions showing strong linkage disequilibrium for this disease have been elucidated through association studies, and a variable number of tandem repeats of the insulin gene (INS VNTR) on chromosome 11p15.5 is associated with susceptibility [3–15]. The INS VNTR region is located 5 ′ upstream of INS and consists of guanine (G)-rich repeat units of 14 – 15 bp of the consensus sequence or slight variations thereof [5,6]. The numbers of repeat units vary markedly in three discrete classes of the INS VNTR: class I (28 – 44 repeat units), class II (45 – 137 Copyright  2010 John Wiley & Sons, Ltd.