M?s?rl? ?ocuklarda Tip 1 Diyabet ile D Vitamini Ba?lay?c? Protein Polimorfizmi Aras?ndaki ?li?ki Yoklu?u

摘要

Background: Type 1 diabetes mellitus (T1D) is a polygenic autoimmune disease. Vitamin D is a potent modulator of the immune system and has been implicated in T1D pathogenesis and prevention. Vitamin D-binding protein (VDBP) is the main systemic transporter of vitamin D and is essential for its cellular endocytosis. Two frequent single nucleotide polymorphisms (SNPs), in exon 11 of the VDBP gene, result in amino acid variants: (rs7041) GAT→GAG substitution replaces aspartic acid by glutamic acid in codon 416; and (rs4588) ACG→AAG substitution in codon 420 leads to an exchange of threonine for lysine. These VDBP variants lead to differences in the affinity for vitamin D. Objective: The objective was to evaluate the association of these 2 VDBP gene SNPs with T1D in Egyptian children. Material and Method: Unrelated 59 children with T1D and 65 healthy controls were included in this study. The sequence of VDBP exon 11, which contains both examined SNPs, was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The frequency of Asp/Glu alleles, at codon 416, was 35.6/64.4% in T1D patients and 44.6/55.4% in controls (P=0.15). At codon 420 the frequency of Thr/Lys alleles were 88.1/11.9% and 87.7/12.3% (P=0.91), respectively. Distributions of genotypes at both loci, and the common haplotypes constructed by them, were also very similar in both groups (P> 0.05). Conclusion: DNA polymorphisms in the VDBP gene are not associated with T1D in Egyptian children.. Turk Jem 2011; 15: 111-5 Giri?: Tip 1 diyabet (T1D), bir poligenik otoimmün hastal?kt?r. D vitamini, immün sistemin gü?lü bir düzenleyicisidir ve T1D patogenezi ve ?nlenmesi ile ili?kilendirilmi?tir. Vitamin D ba?lay?c? protein (VDBP), D vitaminin temel sistemik ta??y?c?s?d?r ve hücresel endositoz i?in gereklidir. VDBP geninde exon 11 ’ de s?k g?rülen iki tek nükleotid polimorfizmi (SNP), amino asit varyantlar?n?n olu?mas?na yol a?ar: (rs7041) GAT → GAG de?i?imi sonucu kodon 416 ’ da glutamik asit yerine aspartik asit ge?er; ve kodon 420 ’ de (rs4588) ACG → AAG de?i?imi ile lizin yerine treoninin ge?er. Bu VDBP varyantlar?, D vitaminine olan affinitede farkl?l?klara yol a?ar. Ama?: Bu ?al??mada M?s?rl? ?ocuklarda, bu iki VDBP geni SNP ’ lerinin T1D ile ili?kisinin ara?t?r?lmas? ama?land?. Metod: Akrabal?k ba?? olmayan 59 T1D ’ li ?ocuk ve 65 sa?l?kl? kontrol ?al??maya dahil edildi. Ara?t?r?lan her iki SNP ’ yi i?eren VDBP exon 11 sekans?, polimeraz zincir reaksiyonu- restriksiyon par?ac?k uzunluk polimorfizmi (PCR-RFLP) y?ntemiyle incelendi. Bulgular: Kodon 416 ’ da Asp/Glu allel s?kl??? T1D hastalar?nda % 35.6 / 64.4 ve kontrollerde % 44.6 /55.4 ?eklindeydi (P=0.15). Kodon 420 ’ de Thr/Lys allel s?kl??? ise s?ras?yla % 88.1/ 11.9 ve % 87.7 / 12.3 tü (P=0.91). Her iki lokustaki genotiplerin ve bunlar?n olu?turdu?u ortak haplotiplerin da??l?m? her iki grupta benzer bulundu (P > 0.05). Sonu?: M?s?rl? ?ocuklarda, VDBP genindeki DNA polimorfizmleri, T1D ile ili?kili bulunmam??t?r. Türk Jem 2011; 15: 111-5