Background
The incidence of type 1 diabetes mellitus (T1DM) in Kuwait is amongst the highest in the world. Vitamin D is considered to be involved in immune modulation and its deficiency contribute to autoimmune destruction of insulin producing beta cells in T1DM patients. Vitamin D has been shown to exert its effects via a nuclear vitamin D receptor (VDR) and therefore,
VDR
gene may be considered a candidate for T1DM susceptibility.
Methods
The genotypes of four
VDR
gene polymorphisms were determined in 253 Kuwaiti Arab T1DM patients and 214 healthy controls by PCR-RFLP analysis. Serum concentrations of three autoantibodies i.e. ICA (Islet cell autoantibody), GADA (Glutamic acid decarboxylase) and INS (Insulin autoantibody) were determined by radio-immunoassays.
Results
Statistically significant differences were detected between the genotypes of two
VDR
gene polymorphisms (
Fok
I, C > T, rs10735810 and
Taq
I, C > T, rs731236) between T1DM patients and controls (
P
< 0.0001). In both, the frequency of variant alleles was considerably high in T1DM than in the controls. In contrast, the
VDR
gene
Apa
I (G > T, rs7975232) and
Bsm
I (A > G, rs1544410) polymorphisms did not show association with T1DM. The homozygous variant genotypes of
Fok
I,
Apa
I and
Taq
I polymorphisms show significant differences between various age-of-onset subgroups while no such association was detected in the case of
Bsm
I polymorphism. Significant differences were also noted between heterozygous genotypes of all four polymorphisms especially between 4-6y and > 6y age-of-onset subgroups of T1DM patients. Three autoantibodies, ICA (Islet cell), GADA (glutamate decarboxylase) and INS (insulin) were positively associated to, varying degrees, with T1DM in Kuwaiti Arabs harboring different
VDR
gene polymorphism genotypes.
Conclusions
Our results demonstrate a significant effect of two
VDR
gene polymorphisms (
Fok
I and
Taq
I) and three autoantibodies on genetic susceptibility of T1DM in Kuwaiti Arabs along with other factors.