Tumor necrosis factor-α allele 2 shows an association with insulin-dependent diabetes mellitus in Latvians

Insulin-dependent diabetes mellitus (IDDM) is one of the most common chronic diseases. It is an autoimmune disease. Genes contributing the most for development of IDDM are located on chromosome 6p21.3 in the region called the major histocompatibility complex (MHC). HLA-DQ8/DR4 and DQ2/DR3 have shown positive association with IDDM, while DQ6 has negative association with IDDM in most Caucasian populations. The location of the tumor necrosis factor alpha (TNF-α) gene in the MHC suggests the role of TNF in the etiology of IDDM as an autoimmune disease. The TNF region contains several polymorphisms that are associated with different levels of TNF-α production and susceptibility to autoimmune and infectious diseases. Ninety-two Latvian IDDM patients corresponding to WHO diagnostic criteria and 107 unrelated age- and sex-matched healthy controls were analyzed for the frequency of TNF-α alleles to test the hypothesis that TNF-α is associated with IDDM. We found that TNF-α microsatellite allele 2 is associated with IDDM, 29/92 (32%), versus 14/107 (13%) in healthy controls. The test of the strongest association of the MICA A5 allele and TNF-α allele 2 with IDDM showed that both are independently associated with the disease.