Diagnostic and prognostic value of polymorphism of candidate genes of secondary osteoporosis in patients with chronic pancreatitis and hypertension

Abstract

Study of features of the combined course of a number of diseases of internal organs is caused by their mutually enhancing negative influence and need to correct diagnostic and therapeutic measures. Among such nosologies, attention is drawn to chronic pancreatitis (CP) and hypertension. Their comorbidity increases a risk of atypical clinical manifestations, torpid to conventional therapy and early development of complications. One of these complications is secondary osteoporosis. Developing structural and functional changes in the bone tissue are not only a compensatory response to an increased need for calcium ions, but also an independent factor in further disease progression when these pathologies are combined. An important role in the diagnosis and prediction of impaired metabolism of bone tissue is played by the study of the polymorphism of candidate genes, which can affect not only the development of osteoporosis, but also determine the timing of this complication to certain extent. Vitamin D (VDR) and lactase (LCT) genes are considered among them.
 Aim of research is to study the role of gene polymorphism of vitamin D receptors (VDR) and lactase gene (LCT) in the risk of developing osteopenic conditions in patients with comorbidity of CP and hypertension.
 Materials and methods. 110 patients with CP were examined, which made it possible to create two groups: main group — 70 people with comorbid CP and hypertension, and comparison group — 40 patients with isolated CP. Control group included 78 healthy individuals. All patients were representative by age and sex. The state of the bone tissue was determined by conducting double-energy X-ray absorptiometry (DEXA). Polymerase chain reaction was used to study the polymorphism of the vitamin D receptor (VDR) and lactase (LCT) genes.
 Results. Majority of patients in the main group (84.3%) had an unfavorable B-allele, in contrast to the comparison group, where this index was equal to 77.5% of cases. Changes in the VDR gene polymorphism, which influenced the frequency of lesions of the osteo-articular system, were stated. Lactose insufficiency (LI) was found out in more than half of the patients with CP (57.5%). Upon comorbidity of CP and hypertension, number of such patients increased (68.6%), which could be considered as a result of impaired vascular pancreatic regulation. At the same time, LI occurred against the background of normal (C/C) polymorphic variants of the LCT gene. Almost a third of patients (35.7%) had osteopenic states, but they were not associated with the lactase gene polymorphism. Comparing the pathological VDR and LCT genes of the entire sample of patients (188 people), we obtained the frequency distribution of a statistically significant nature (CCP, χ2=21.92547, df=4, p=0.00021). Namely, the coincidence of Bb and CT heterozygotes was 37.88%, and that of BB and CC homozygotes was 45.57%. The coincidence of Bb and CC was 21.21%, BB and CT — 31.65%. Frequency distribution in patients with isolated CP (40) also had a statistically significant character (CCP, χ2=10.69637, df=4, p=0.03020). Coincidence in the heterozygote of Bb and CT was 25%, and that of homozygotes for BB and CC — 60%. Distribution of BB and CC corresponded to 31.25%, BB and CT — 33.33%.
 Conclusion. It was stated that upon CP, as well as in its comorbidity with hypertension, osteoporotic conditions might be formed. Combination of calcium-dependent diseases (CP and hypertension) and the vitamin D receptors gene polymorphism with a predominance of unfavorable B-allele could be the cause of such conditions. At the same time, the risk of developing osteoporotic conditions increases 4 times. Course of CP is often accompanied by LI, which may be the result of both gene aberrations and loss of lactase-secreting function in a given disease.