Vitamin D receptor polymorphism and susceptibility to type 1 diabetes in the Dalmatian population Veselin S ˇ krabic ´ a,1 , Tatijana Zemunik b,1 , Marjan S ˇ itum b , Janos ˇ Terzic ´ b,  a Department of Pediatrics, Clinical Hospital Split, Split, Croatia b Departments of Biology and Physiology, Split University School of Medicine, S ˇ oltanska 2, 21000 Split, Croatia Received 30 April 2002; received in revised form 19 July 2002; accepted 5 August 2002 Abstract Several studies have found a relationship between polymorphisms of the vitamin D receptor gene (VDR) and development of type 1 diabetes (T1DM). The meaning of this observation remains unclear and its relevance must be checked in different population samples. To examine the association of VDR polymorphisms and susceptibility to T1DM in the Dalmatian population of South Croatia we studied 134 individuals with type 1 diabetes and 132 control subjects. VDR genotyping was performed using PCR and Bsm I, Apa I and Taq I restriction enzymes. Data were analysed using the x 2 -test. The genotype combination which conferred strongest susceptibility to T1DM was BBAAtt (P /0.002). Interestingly, the BAt haplotype was found to be a risk factor in a German population, the only European population tested thus far. Our results indicate that VDR polymorphisms are associated with increased risk of T1DM in the Dalmatian population of South Croatia and warrant further studies. # 2002 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Vitamin D receptor; Genotype; Type 1 diabetes; Genetic susceptibility; Dalmatia 1. Introduction Type 1 or insulin dependent diabetes mellitus (T1DM) is an autoimmune disease with a strong genetic component [1  /3]. An autoimmune attack on pancreatic beta cells is mediated by autoreac- tive T cells and apoptosis-inducing cytokines and results in termination of insulin production [4  /6]. The main genetic contribution to T1DM suscept- ibility lies within the major histocompatibility complex (MHC) [7]. Non-MHC chromosomal regions are also involved, particularly the regula- tory region of the insulin gene and the interleukin- 1 receptor type 1 gene [3,8  /11]. Recently, a relationship between the vitamin D receptor (VDR) gene and T1DM has been noted in several populations [12 /15]. Although, the exact nature of VDR involvement in T1DM is unknown, this relationship is not surprising and is supported by three lines of evidence. First, vitamin D has immunosuppressive effects via inhibition of lym- phocyte activation and cytokine production [16,17]. Second, infants who received supplements  Corresponding author. Tel.:  /385-21-557-944; fax:  /385- 21-557-955 E-mail address: jterzic@bsb.mefst.hr (J. Terzic ´). 1 Authors equally contributed to the study. Diabetes Research and Clinical Practice 59 (2003) 31 /35 www.elsevier.com/locate/diabres 0168-8227/02/$ - see front matter # 2002 Elsevier Science Ireland Ltd. All rights reserved. PII:S0168-8227(02)00195-X