Genetic studies:
Genetic variations in the genes of vitamin D synthesis and its metabolism have been linked with many diseases in the world populations (114, 115, 116).
Vitamin D receptor (VDR) is a type of nuclear receptor that after binding its ligand calcitriol (active form of vitamin D) regulates expression of many genes (117, 118). The variations in the VDR gene have been associated with several disease conditions in different populations (119, 120, 121, 122).
Many studies in Pakistani population showed the association of some diseases with certain types of SNPs in VDR gene. The Apa1 SNP present in the 3สน intronic region of VDR may affects the stability of mRNA of VDR (123). Some SNPs in VDR gene were found to be associated with Type 1 diabetes (T1D) (124). Another study was conducted to probe a link between T1D and two SNPs of VDR (Fok1 and Apa1) in children (125). The results of this study showed vitamin D deficiency was prevalent in studied group but no significant association was found of any of these SNPs with T1D. It may be due to very small sample size (44 cases and 44 controls).
SNPs in VDR gene have been studied with the relevance of vitamin D levels in healthy women of Pakistani population (126). Two SNPs (Fok1 and Taq1) were found significantly associated with vitamin D deficiency and insufficiency.
Vitamin D circulates in the body after binding with vitamin D binding protein (VDBP); a type of transporter protein (127). A case control study showed significant association of group-specific 1-2 (Gc 1-2) genotype with the risk of T2DM in the subjects (128). Another study found a significant link between vitamin D deficiency and IF-IF genotype of VDBP gene with acute myocardial infarction (AMI) in Pakistani population (74). Breast cancer is quite prevalent in Pakistani women (83). The analyses of 360,933 breast cancer cases revealed that Asian Pakistani/Indian women had higher frequency of breast cancer than Caucasians (129). Meta analyses of some studies carried out to probe the role of variation in VDR gene with the onset of breast cancer, showed its positive correlation in different world populations (130). Many studies in Pakistani population revealed the association of variations in VDR gene with breast cancer. A case-control study (103 cases and 161 controls) showed the GG genotype of cdx-2 SNP may increase the risk of breast cancer in young females belonged to the Southern Punjab (131). The Tru9I SNP in VDR gene was studied in 228 patients and 503 controls and found that this SNP could be associated with the risk of this disease (132). It found from the same study that the mutant Tru9I was found significantly associated with grade IV carcinoma in the study group.
The b allele of Bsm1 polymorphism of VDR gene showed positive association with breast cancer (133). This study included 463 cases with known BRCA1/2 status and 1012 controls. Sub-group analysis of the study revealed that BRCA1/2 non-carriers and subjects with a family history of breast and/or ovarian cancer had significant association of this allele with this disease condition.
The overall results of many studies showed that the variations in VDR gene are not associated with some disease conditions in Pakistani population. The results of a study conducted by our group showed that only TT genotype of TaqI polymorphism was significantly associated with T2DM in Karachi, Pakistan (Mahmood et al., unpublished data).