Association of 25 (OH)-D3 Level With the CYP27B1 rs10877012 Variants and Metabolic Parameters in T2DM Patients From Kurdistan, Iraq

Abstract

Background:There is an increasing prevalence of type 2 diabetes mellitus (T2DM) worldwide. The deficiency of vitamin D is a worldwide health problem that can increase susceptibility to T2DM. Cytochrome P450 family 27 subfamily B member 1 (CYP27B1) encodes the enzyme 1α-hydroxylase in the kidney, which converts 25 (OH)-D3 to 1,25 (OH)2-D3. The CYP27B1 rs10877012 G/T polymorphism is located in the gene promoter and can influence vitamin D3 level. Objectives: This study aimed to investigate the relationship between CYP27B1 gene polymorphism and the 25 (OH)-D3 serum level and the risk of T2DM. Additionally, the effect of 25 (OH)-D3 level on metabolic parameters was investigated. Methods: We investigated 310 individuals including 205 T2DM patients and 105 healthy subjects from the city of AL-Sulaymaniyah, Kurdistan of Iraq. The CYP27B1 gene variants were identified by the polymerase chain reaction followed by digestion with HinfI restriction enzyme. Results: The mean level of 25 (OH)-D3 was 18.4±8.5 ng/mL in T2DM patients and 24.1±9.3 ng/mL in healthy controls (P<0.001). Significantly higher body mass index (BMI), HbA1c level, and fasting blood sugar concentration were detected in individuals with vitamin D insufficiency (P=0.009, P=0.001, and P=0.01, respectively) and vitamin D deficiency (P=0.025, P<0.001, and P<0.001, respectively) compared to those with a sufficient level of vitamin D. The T allele frequency of CYP27B1 was 38.1% in controls and 40.2% in patients (P=0.6). In the presence of the GT genotype, a significantly lower level of 25 (OH)-D3 was obtained compared to the GG genotype (P=0.02) among the patients. Conclusion: We found that the CYP27B1 rs10877012 polymorphism was not a risk factor for T2DM but it affected the level of 25 (OH)-D3 in diabetic patients and vitamin D deficiency and insufficiency increased the values of BMI, HbA1c, and FBS as the metabolic parameters involved in the development of T2DM.