Association of RAGE gene polymorphisms (rs2070600 and rs2071288) withbone metabolism disturbances in patients with chronic kidney disease

Document Type : Original Article

Authors
Asma Ali Awad 1
Gholamreza Dehghan 1 , 2
Hamid Tayebi Khosroshahi 3
Mahdi Haghi 1
1 Laboratory of Biochemistry and Molecular Biology, Department of Biology, Faculty of Natural Sciences, University of Tabriz, Tabriz, Iran.
2 Research Center of Biosciences and Biotechnology (RCBB), University of Tabriz, Tabriz, Iran.
3  Department of Nephrology, Tabriz University of Medical Sciences, Tabriz, Iran.
‎10.22088/IJMCM.BUMS.14.4.1045
Abstract
Chronic kidney disease (CKD) is frequently accompanied by disturbances in bone
metabolism, leading to a heightened risk of fractures. The receptor for advanced
glycation end-products (RAGE) plays a pivotal role in the pathogenesis of CKD. This
case-control study included 50 CKD patients and 50 healthy controls to examine the
association between RAGE gene polymorphisms (rs2070600 and rs2071288) and bone
metabolism markers. Serum parathyroid hormone (PTH), alkaline phosphatase (ALP),
and vitamin D levels were measured as indicators of bone metabolism. CKD patients
exhibited significantly higher ALP (317.54 ± 21.95 U/L) and PTH (331.33 ± 17.11
pg/mL) levels, along with lower vitamin D (26.92 ± 6.64 ng/mL) compared to controls
(all P < 0.05). The CC genotype of rs2070600 was more prevalent among patients (52%)
and was associated with an increased risk of CKD (OR = 2.79, 95% CI: 1.21–6.39,
P = 0.014). In contrast, no significant association was found between rs2071288 and
CKD risk. Notably, individuals carrying CC or CT genotypes for rs2070600 and
rs2071288 had higher levels of PTH and ALP, alongside significantly lower levels of
vitamin D. The RAGE gene's rs2070600 polymorphism may be connected to
abnormalities in bone metabolism and the advancement of CKD. These results indicate
that rs2070600 genotyping may be useful in identifying high-risk patients; however,
additional research is required to validate its clinical significance.
Keywords
Chronic kidney disease
Bone metabolism markers
Genetic polymorphism
Receptors for advanced glycation end products