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Proceedings of Scientific Meeting Genetic Predisposition to IDDM at the Insulin-Gene Linked Polymorphic Region, IDDM2, is Different between Chinese and Caucasians PT Cheung, LCK Low, BR Hawkins, KCB Tan, EYW Kwan, KSL Lam, V Chan
Background: IDDM is a disease with polygenic inheritance. Understanding the genetic risk factors for IDDM may enable clinicians to identify high risk subjects for potential preventive therapy. We and others have found different class II HLA susceptibility in Chinese IDDM patients. Aim: To define potential genetic susceptibility factors for local Chinese population at the insulin-gene linked polymorphic region with respect to the reported risk conferring polymorphisms in Caucasians. These were class I variable number of tandem repeats (VNTR), the presence of -23/HphI and absence of +1127/PstI, +1428/FokI and +805/DraIII cut sites. Subjects: 52 IDDM patients with onset of disease below 15 years old, 54 IDDM patients with onset above 15 years old and 57 controls were studied. Methods: Southern blot hybridisation was used to identify the classes I-III alleles of the variable number of tandem repeats (VNTR). PCR-RFLP was used to study the polymorphic sites in the insulin. The detailed sizing of the VNTR class I alleles was determined by fluorescence-based PCR genotyping with an ABI Prism 373 DNA sequencer. Results: Over 95 % of the studied subjects have the alpha allele for the insulin gene as reflected by the presence of-23/HphI and absence of +1127/PstI, +1428/FokI and +805/DraIII cut sites. They all have class I VNTR alleles, known to be linked with presence of HphI cut site and increased IDDM risk in Caucasians. We did not observe any difference in the prevalence of these known IDDM susceptibility polymorphisms between IDDM patients and the controls. Detailed sizing by fluorescence-based PCR genotyping revealed that the distribution of the class I VNTR repeat numbers in Chinese subjects was totally different from those reported in Caucasians. Conclusions: (1) The presence of Class I VNTR alone is not a risk factor for developing IDDM in Chinese. (2) The detailed distribution in the class I VNTR alleles in Chinese is totally different from Caucasians. (3) The nucleotide sequences constituting the VNTR repeats in Chinese have to be analysed. |