CYP27B1 Gene Polymorphism Is Associated With Autoimmune Thyroid Diseases

Objective:1,25-Dihyroxyvitamin D3 [1,25(OH)2D3]---the most active natural vitamin D metabolite, has important immunomodulatory properties. CYP27B1 (25-hydroxyvitamin D3-1α-hydroxylase) is a mitochondrial P450 enzyme , which catalyzes the conversion of 25-hydroxyvitamin D3 to 1,25(OH)2D3. It is the key enzyme for controlling the rate of 1,25(OH)2D3 production. A CYP27B1 polymorphism could affect systemic or tissue-specific 1,25(OH)2D3 levels. Several studies recently presume that the CYP27B1 polymorphism is associated with the predisposition of the autoimmune thyroid disease in European. So we choose two gene sites -1260 and +2838 to investigate the relationship between CYP27B1 gene polymorphism and autoimmune thyroid diseases in Chinese Han nationality.Methods:1. A case-control study including 158 patients with GD, 174 patients with HT and 172 matched controls was conducted. Three genotypes of CYP27 B1 gene -1260 site (CC,AA and AC) were determined by polymerase chain reaction--restriction fragment length polymorphism (PCR-RFLP) assay and confirmed by sequencing. 2. A case-control study including 172 patients with GD, 180 patients with HT and 197 matched controls was conducted. Three genotypes of CYP27B1 gene +2838 site (TT,TC and CC) were determined by polymerase chain reaction--polymerase chain reaction-sequence specific primer (PCR-SSP) assay and confirmed by sequencing.Results:1. The genotypic distribution of CYP27 B1 gene -1260 site didn't deviate from Hardy-Weinberg equilibrium. In the control group, the genotype frequencies and allele frequencies of -1260A/C were CC34.3%, AA19.2 % , AC46.5 % , C57.6 % , A42.4 % . while the corresponding frequencies in the Graves'disease group were 48.1%, 13.3%, 38.6%, 67.4%, 32.6% and in the Hashimoto's thyroiditis group were 47.1%, 10.3%, 42.5%, 68.4%, 31.6%, respectively. There was significant difference in the genotypes and alleles in -1260A/C polymorphism between GD or HT and control group(GD: genotype frequenciesχ2=6.879, P=0.034, allele frequenciesχ2=6.798, P=0.009; HT: genotype frequenciesχ2=8.386, P=0.065, allele frequenciesχ2=8.709, P=0.003).2. The genotypic distribution of CYP27 B1 gene +2838 site didn't deviate from Hardy-Weinberg equilibrium. In the control group, the genotype frequencies and allele frequencies of +2838T/C were TT56.9%, TC34.5 % , CC8.6 % , T74.1 % , C25.9 % . while the corresponding frequencies in the Graves'disease group were 73.8%, 23.3%, 2.9%, 85.5 %, 14.5% and in the Hashimoto's thyroiditis group were 66.7%, 32.2%, 1.1%, 82.8%, 17.2%, respectively. There was significant difference in the genotypes and alleles in +2838T/C polymorphism between GD or HT and control group ( GD: genotype frequenciesχ2=13.113, P=0.001, allele frequenciesχ2=14.475, P=0.0001; HT: genotype frequenciesχ2=12.107, P=0.002; allele frequenciesχ2=8.301, P=0.004).Conclusion:The polymorphisms of CYP27B1 promoter -1260A/C and +2838T/C in intron 6 are associated with susceptibility to GD or HT in Chinese Han nationality. The alternate alleles CYP27B1-1260A, +2838C might confer protection.