Association analysis of the COL1A1 polymorphism with bone mineral density and prevalent fractures in Polish postmenopausal women with osteoporosis

Abstract

IntroductionPolymorphism in the promoter region of collagen type 1α (COL1A1) +1245G/T (Sp1, rs1800012) was in some studies shown to be relevant for bone mineral density (BMD) and low-energy fracture prediction. The aim of the study was to confirm this finding in a group of postmenopausal women diagnosed with osteoporosis.Material and methodsWe investigated 311 Caucasian women (mean age: 65.2 ±9.39 years) either after low-energy fractures (regardless of the location) or meeting World Health Organization (WHO) criteria for osteoporosis. All patients underwent clinical examination in order to exclude secondary osteoporosis; hip and lumbar spine DEXA was performed (Lunar). The three genotypes of Sp1 polymorphism were determined by RFLP (restriction fragment length polymorphism).ResultsDistribution of COL1A1 genotypes (SS/Ss/ss) agreed with Hardy-Weinberg equilibrium. No relation between COL1A1 genotypes and hip/L1-L4 BMD was found. Fractures were reported in 26.3% of women. Prevalence of low-energy fractures, regardless of the type, was 50.0% in ss genotype carriers, 26.4% in SS homozygotes and 23.7% in Ss heterozygotes. There was no statistically significant recessive or dominant effect of any Sp1 genotype on fracture prevalence (p = 0.613).ConclusionsWe failed to observe that COL1A1 Sp 1 genotypes contribute to BMD determination or are associated with prevalent low-energy fractures in a Polish cohort of postmenopausal osteoporotic women.

Evaluation of the Genetic Association and mRNA Expression of the COL1A1, BMP2, and BMP4 Genes in the Development of Otosclerosis

“…We selected these four COL1A1 variants because they were previously reported to contribute to various musculoskeletal diseases and bone remodeling. For instance, rs1800012 in the COL1A1 gene has been linked to osteoarthritis and intervertebral disk degeneration (Zhong et al, 2017); in addition, this polymorphism is located within the Sp1 transcription factor binding site in intron 1 that has been shown to influence bone mineral density and the prevalence of fractures in postmenopausal women with osteoporosis (Dytfeld et al, 2016). Within this study, we showed that rs1800012 is significantly associated with OTSC.…”

Integrated Bioinformatic Analysis of the Shared Molecular Mechanisms Between Osteoporosis and Atherosclerosis

“…COL1A1 is mainly involved in bone matrix formation, coding for collagen type 1 which is the most abundant extracellular protein in bone and serves as an indicator of bone formation (58). Mutations in COL1A1 gene have been demonstrated to be responsible for the autosomal dominant form of osteogenesis imperfecta, with severe osteoporosis (59). Studies have confirmed that COL1A1 is overexpressed in artery at animals with atherogenic diet and the increase was contributed to the inflammatory process and the activate the cytokine TGF-b, which supports the fibrotic process through expressing COL1A1 (60).…”

Col1a1 Gene Sp1 Polymorphism and Osteoporosis Risk in Postmenopausal Women

“…Вместе с тем следует указать, что в отдельных работах вышеуказанного влияния полиморфизма Sp1 гена COL1A1 на раз-витие остеопороза и/или на возникновение низко-энергетических переломов все-таки установлено не было [6,8,10]. Отсутствие доказательств роли вы-шеуказанного полиморфизма в развитии остеопо-роза и его осложнений в последних исследованиях объясняется, по всей видимости, сложностью этио-патогенеза заболевания.…”

“…В большинстве выполненных к на-стоящему времени работ отмечается влияние вы-шеуказанного полиморфизма на показатели мине-ральной плотности костной ткани, риск развития остеопороза и/или возникновения низкоэнергети-ческих переломов [8]. В других же работах выше-указанная роль полиморфизма Sp1 гена COL1A1 подтверждения не нашла [6,10]. В странах СНГ внимание данной проблеме уделено недостаточ-но, а имеющиеся единичные публикации [1,4] не позволяют сделать достаточно обоснованные выводы.…”