SUMO4 M55V polymorphism affects susceptibility to type I diabetes in HLA DR3- and DR4-positive Swedish patients

Abstract

SUMO4 M55V, located in IDDM5, has been a focus for debate because of its association to type I diabetes (TIDM) in Asians but not in Caucasians. The current study aims to test the significance of M55V association to TIDM in a large cohort of Swedish Caucasians, and to test whether M55V is associated in those carrying human leukocyte antigen (HLA) class II molecules. A total of 673 TIDM patients and 535 age-and sex-matched healthy controls were included in the study. PCR-RFLP was performed to identify the genotype and allele variations. Our data suggest that SUMO4 M55V is not associated with susceptibility to TIDM by itself. When we stratified our patients and controls based on heterozygosity for HLA-DR3/DR4 and SUMO4 genotypes, we found that presence of SUMO4 GG increased further the relative risk conferred by HLA-DR3/DR4 to TIDM, whereas SUMO4 AA decreased the risk. From the current study, we conclude that SUMO4 M55V is associated with TIDM in association with high-risk HLA-DR3 and DR4, but not by itself.

Identification of New Susceptibility Genes for Type 1 Diabetes: An Update

“…In Caucasians, the analyses of SUMO4 association with T1D produced negative results [67][68][69][70] with the exception of the dataset from North-Central Florida in the US [62,71]. In Swedish patients only, the M55 variant was not associated with diabetes by itself but increased the risk in the subset positive for the high-risk HLA-DR3/DR4 [72]. Hence, the SUMO4 M55V polymorphism seems to be specifically associated with T1D in Asians.…”

Posttranslational Protein Modifications in Type 1 Diabetes - Genetic Studies with PCMT1, the Repair Enzyme Protein Isoaspartate Methyltransferase (PIMT) Encoding Gene

“…Nevertheless, as with other minor genes involved in the pathogenesis of T1D, its effect might not be significant on its own, but only through interaction with other genes, as suggested by a recent Swedish study. This work showed a positive association between the functional SUMO4 variant and T1D in highrisk HLA DR3/DR4 subjects [23].…”

Association between the SUMO4 M55V (A163G) polymorphism and susceptibility to type 1 diabetes: A meta-analysis

“…Seven reports were excluded because they contained family data [23][24][25][26], duplicated data [9], and data not in HWE [7,27], and thus, eight reports met the inclusion criteria [3,6,8,[10][11][12][13][14]. However, one study had data on three different groups [8], and one study included five different groups [3], and we analyzed these groups independently.…”

“…Fifty-eight studies were identified by electronic and manual searching and 15 were selected for a full-text review based on title and abstract details [3,[6][7][8][9][10][11][12][13][14][23][24][25][26][27]. Seven reports were excluded because they contained family data [23][24][25][26], duplicated data [9], and data not in HWE [7,27], and thus, eight reports met the inclusion criteria [3,6,8,[10][11][12][13][14].…”

“…Several articles have reported an association between the SUMO4 M55V polymorphism and T1D, but by no means in all [3,[6][7][8][9][10][11][12][13][14]. The reasons for this disparity may be small sample sizes, low statistical power, and/or clinical heterogeneity, and therefore, to overcome the limitations of individual studies, resolve inconsistencies, and reduce the likelihood that random errors are responsible for false-positive or false-negative associations [15][16][17], we turned to meta-analysis.…”