Title of thesis: Association of selected polymorphisms in the VDR gene and BMD among Palestinian Type 1 diabetes Mellitus patients رسالة ماجستير

Abstract

Objectives: The aims of this investigation was to study the association between the in VDR gene polymorphisms including rs10735810 (exon 2) and rs1544410 (intron 8), BMD and osteoporosis in type 1 diabetes mellitus and its significance in the pathophysiology of type 1 diabetes. Materials and methods: A 88 healthy control and 86 diabetic patients aged 18-30 years where recruited in this study. All subjects were exposed for bone mineral density (BMD) examination using DEXA scan in three main locations ( femur neck, total hip and lumber spine L1- L4). Genomic DNA was prepared from whole blood samples obtained from all subject. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was ultimately used to determine the distribution of the various genotypes and haplotypes in rs10735810 (exon 2) and rs1544410 (intron 8). Comprehensive statistical analysis to correlate between the indicated haplotypes and genotypes in the VDR gene with type 1 diabetes and BMD in the various locations and osteoporosis was performed using SPSS program. Results: Our data confirmed a strong association between type 1 diabetes, BMD, and total osteoporosis. The data evidently showed that (rs10735810 (exon 2) but not rs1544410 (intron 8) was associated with lower BMD and osteoporosis status at the indicated sites. The data also showed no association between rs10735810 (exon 2) and rs1544410 (intron 8) haplotypes and genotypes with diabetes. However, it showed significant association of rs10735810 (exon 2) C allele as a risk of osteoporosis and the T as protective allele with negative between the various alleles in rs1544410 (intron 8) and osteoporosis. Furthermore, the data showed rs10735810 (exon 2) but not rs1544410 (intron 8) alleles represent causative factor of low BMD and osteoporosis but is not linked to in diabetes type 1 patients, The cause of osteoporosis in diabetic vi type 1 patients might be due to other genetic factors and/or to environmental factors including vitamin D status and other nutritional factors. Conclusions: 1- Strong association between type 1 diabetes, BMD and total osteoporosis is confirmed. 2- Evidently, variants in rs10735810 (exon 2) but not rs1544410 (intron 8) was associated with lower BMD and osteoporosis status at the indicated sites. 3- No association between rs10735810 (exon 2) and rs1544410 (intron 8) haplotypes and genotypes with diabetes was detected. 4- Significant association between rs10735810 (exon 2) C allele as a risk of osteoporosis and the T as protective allele with negative between the various alleles in rs1544410 (intron 8) and osteoporosis was evident. 5- The data showed rs10735810 (exon 2) but not rs1544410 (intron 8) alleles is associated with low BMD and osteoporosis but not linked to diabetes type 1. 6- The cause of osteoporosis in diabetic type 1 patients might be due to other genetic factors and/or to environmental factors including vitamin D status and other nutritional factors.