تأثير تعدد الأشكال الجينية لمستقبل فيتامين D3 في النساء العراقيات بعد سن اليأس المصابات بهشاشة العظام وارتباطها ببعض الدالات الكيموحيوية

The Impact of Vitamin D3 Receptor Gene Polymorphism in Iraqi Post-Menopausal Women with Osteoporosis and their Association with Some Biochemical Markers

A skeletal disorder known as osteoporosis (OP) is characterized by decreased bone mass, deteriorating bone tissue microarchitecture, and an increase in fragility fractures. Osteoporosis is a serious problem in public health that affects millions of people, mainly postmenopausal women. Postmenopausal osteoporosis is further influenced by factors such as age, body mass index (BMI), smoking, alcohol use, physical activity, prolonged calcium and vitamin D consumption, pregnancy interval, age of pregnancy, multiple births, age of menarche, and menopause status. Diabetes mellitus and osteoporosis are two frequent medical conditions that are growing more prevalent in older people. The presented work aimed to studying the genetic variation of the VDR gene (rs731236) in Iraqi postmenopausal women with osteoporosis and then investigates its function in the pathophysiology of osteoporosis to study the association between [25(OH)D3], estrogens, parathyroid hormone (PTH), total alkaline phosphatase (ALP) activity, and bone mineral density in postmenopausal women with and without type 2 diabetic. A cross-sectional study was conducted on 60 postmenopausal women with osteoporosis with age ranged between 55-80 years, divided into 30 of type 2 diabetic women and 30 without type 2 diabetes mellitus, the third group include 50 apparently healthy postmenopausal women. Patients with osteoporosis were randomly selected from the fragility examination unit of Al-Hussein Medical Hospital, Kerbala health directorates / Kerbala – Iraq between Nov., 2021 to June, 2022. From each sample the body mass index (BMI) was measured, 5 ml of venous whole blood was placed in gel tube and centrifuge at 2000 x g for 10 min. to obtained the serum and kept until the time of determination of [25(OH)D3], parathyroid hormone (PTH), estradiol by immunoassay analysis using Cobas e411 analyzer. total alkaline phosphatase activity was determined by chemistry analyzer Smart 120T/H. T-score and bone mineral density by Dual Energy X-ray absorptiometry scan (DEXA) at lumbar spine regions (L1–L4 vertebrae) which confirmed postmenopausal osteoporosis, the genotypes and allele frequencies of VDR variants were determined by polymerase chain reaction-allele specific using DNA isolated from peripheral blood.
The polymorphisms were detected using PCR – Allele-specific, the amplification of the VDR gene (rs 731236) SNP which were classified into three genotypes the major genotype group (TT) homozygous for the allele T, the minor genotype group (CC) homozygous for the allele C Heterozygous (TC). Genotype frequencies of the (rs 731236) polymorphism were are not consistent with Hardy–Weinberg equilibrium (HWE). Allele frequencies were 62%, 18% and 20% for TT, TC and CC, respectively, in control group. The Heterozygous (TC) and homozygous genotype (CC) significantly increased the risk, Regarding the results of parameters showed that in postmenopausal women an increased bone resorption associated with significant differences (p<0.05) with age, and it was proved that significant decrease (p<0.01) in bone mineral density, t-scores for dual energy X-ray absorptiometry scan, and decrease in Vitamin D (p<0.05) , The obtained data showed negative Correlations between 25(OH)D3with both Age , BMI, PTH , ALP of women with OP, while there are positive correlations between Vitamin D3 with estrogen and progesterone. This study found that osteoporosis incidence and T-score values are significantly greater in postmenopausal women with type 2 diabetes than in those without. The prevalence of vitamin D deficiency is higher in postmenopausal T2DM women (76.67%) than in non-diabetic postmenopausal women (63.33%), despite the fact that both diabetic and non-diabetic women have high levels of the vitamin. Variation in the VDR TaqI was found to be a significant deciding risk factor for osteoporosis progression in the group of postmenopausal women in Iraq.