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MINISTRY OF EDUCATION AND TRAINING MINISTRY OF HEALTH HANOI MEDICAL UNIVERSITY TRAN PHUONG HAI POLYMORPHISM OF SOME GENES IN RELATION TO OSTEOPOROTIC VERTEBRAL FRACTURE IN POSTMENOPAUSAL WOMEN Major I[.]
MINISTRY OF EDUCATION MINISTRY OF HEALTH AND TRAINING HANOI MEDICAL UNIVERSITY TRAN PHUONG HAI POLYMORPHISM OF SOME GENES IN RELATION TO OSTEOPOROTIC VERTEBRAL FRACTURE IN POSTMENOPAUSAL WOMEN Major : Internal Medicine- Rheumatology Code number : 9720107 SUMMARY OF PhD THESIS HANOI – 2022 THIS THESIS WAS COMPLETED AT HANOI MEDICAL UNIVERSITY Supervisor: Nguyen Thi Thanh Huong, MD, PhD Tran Thi To Chau, MD, PhD Reviewer 1: Reviewer 2: Reviewer 3: My thesis will be presented to The Committee at HaNoi Medical University on …… Where to find the thesis: + National Library of VietNam + HaNoi Medical University’s library INTRODUCTION Osteoporosis is a health condition that bone mineral density and bone quality reduce, leading to increased fracture susceptibility, causing to bone fractures, disability, and mortality Osteoporosis is more common in post-menopausal women since bone loss significantly aggravates in this period According to statistics of the International Osteoporosis Foundation (IOF), 50% of postmenopausal women aged over 50 are at risk of osteoporotic breakages, of which 26% have vertebral body fractures The current guideline is to early treat patients having both low bone mineral density and fracture risk factors Identifying fracture risk factors individually plays an essential role in taking early intervention to reach treatment’s goals and taper fractures risk Generally, risk factors for osteoporosis and fractures have been identified such as age, gender, race, body mass index, bone mineral density, etc Genes related to the risk of osteoporotic fractures have been proven through many studies So far, on the world gene map, 203 genes related to bone mineral density have been published, including 14 genes associated with fracture risk (p< 5x10-4) Many studies in Europe and Asia have shown a relationship between genes and osteoporotic fractures Of these, genes (MTHFR at SNP rs1801133, LRP5 at SNP rs41494349, FTO at SNP rs11211980) were shown to be associated with the risk of osteoporosis and osteoporosis-related fractures, however, the results were heterogeneous between races In 2011, H Wang et al analyzed 20 studies that showed a mild correlation between SNP rs1801133 MTHFR and bone mineral density and fracture risk In 2013, Bich Tran found that FTO SNP rs1121980 gene carriers had an increased risk of osteoporosis fractures by times Research in China has shown that the LRP5 gene is associated with an elevated risk of fractures and osteoporosis In the Vietnamese population, this is the first study to analyze the relationship between genes and the risk of osteoporotic vertebral body fracture in postmenopausal women At the same time, the research results will contribute further data to enrich the Vietnamese genetic map of osteoporosis Therefore, the study "Polymorphism of some genes in relation to osteoporotic vertebral fracture in postmenopausal women” was carried out with two objectives: To describe the characteristics of vertebral fracture (vertebral body fracture) due to osteoporosis in postmenopausal women and some related factors To analyze the polymorphisms of the MTHFR (rs1801133), LRP5 (rs41494349) and FTO (rs11211980) genes and their relationship with osteoporosis- related vertebral body fractures in postmenopausal women NEW CONTRIBUTION OF THE THESIS The study conducted a survey on the rate of vertebral body fractures due to osteoporosis in postmenopausal women and analyzed the risk factors The grade I fracture rate was 7.2% and the grade II was 10.6% Common fracture sites are at T12, L1 to L3 Compression fractures accounted for the highest rate (43%), followed by wedge and biconcavity fractures Factors affecting the risk of osteoporosis-related vertebral fracture in postmenopausal women are: age≥ 60 years, BMI< 18.5 kg/m2, menopause duration ≥ 10 years, patients have >3 children, physical activity level < 600 METs-min/week and osteoporosis While analyzing the polymorphisms of genes: MTHFR (rs1801133), LRP5 (rs41494349) and FTO (rs11211980), we found a relationship between the MTHFR genotype (rs1801133) and the rate of vertebral fractures (p 0.05 Subgroup of patients aged ≥ 60 years had fracture risk 3.597 times higher than that aged 0.05) Thus, in some research on osteoporosis and osteoporotic fractures in VietNam as well as in the world, participants are mainly the elderly, for example, women aged over 60 Globally, in many countries, the elderly is defined as people aged over 65, that means years older than the elderly according to Vietnamese law 4.2.3.2 Height, weight, body mass index in relation to vertebral body fractures Osteoporotic vertebral body fractures are affected by a variety of factors, including anthropometric features Height is a factor influencing BMD Short stature adults have lower bone mass, so they are more likely to have osteoporosis and fractures In our study, the group of patients with vertebral body breakages had an average height of 150 cm, which was statistically significantly lower than that of the non- VBF group (152 cm) with p value < 0.05 This result is similar to the L.Bennani’s findings The author studied 288 postmenopausal women and found that the average height of the VBF group was cm (0.26 - 3.3) lower than that of the non-VBF group (0.26 - 3.3) compared to 96 cm (0.33 – 2.4), p 0.05 The age at menopause in our study is similar to that in Tran Thi To Chau's study, which the average age at menopause of rural women in the North is 47± years old Besides, this number in the research by Hoang Van Dung is 47.7 ± 3.8 years old In China, the average age at menopause for urban and rural women is 49.5 and 47.5 years, respectively 4.2.3.4 Reproductive status and vertebral body fractures Pregnancy can increase the effect and action of hormones on BMD Some studies have found that in women who gave birth to too many children, there may also be an elevated risk of osteoporosis due to inadequate nutrition and intake of calcium - vitamin D Our research results show that the risk of vertebral body fracture in women who had more than children is 2.205 times higher than that in women having less than children with OR: 2,205 (95% CI: 1.627-3,665); p < 0.05 In multivariable regression analysis with factors such as age, BMI, duration of menopause, number of children and level of physical activity, we did not detect any significant effect of number of children on vertebral body fratucres (p > 0.05) 4.2.3.5 Physical activity level and vertebral body fracture Decreased activity in the elderly is also a risk factor for bone loss The muscular movement stimulates bone formation and increases bone mass, while exercise also helps rise muscle strength and reduce the fall hazard Conversely, reduced mobility leads to rapid bone loss According to a study by Feskanich D in 2002 in the US on 61,000 postmenopausal women, participants who walked at least hours/week cut down the risk of femoral neck fractures by 40% compared with the group who walked less than hour/ week RR = 0.6, 95%CI: 0.4-0.9) However, excessive exercise, prolonged and strenuous physical labor, inadequate nutrition, weight loss, and reduction of total body fat will lead to an extensive risk of osteoporosis and fractures 4.2.3.6 Bone mineral density and vertebral body fractures In this study, the relationship between bone density in both spine and femoral neck of the fracture group was lower than that of the non-fracture group (p< 0.05) The deviation of bone density in spine was more obvious than that in femoral neck This is consistent with previous evidences, which confirming a correlation between bone density and fracture risk, particularly at the spine For each standard deviation decrease in BMD at lumbar vertebrae, the risk of a new vertebral body fracture increases to times Cauley J.A et al., in a longitudinal cohort study of 2680 Caucasian women in the United States for 15 years, the authors showed that a 1-standard deviation decrease in BMD at the femoral neck intensifies the likelihood of fractures in the vertebral body up 1.78 times 4.3 Polymorphisms of MTHFR, FTO, LRP5 genes in relation to osteoporosis-induced vertebral body fracture in postmenopausal women ... relationship between genetic polymorphisms and osteoporotic vertebral body fracture FTO gene at SNP rs1121980 Rate of CC genotype % Continuous Rate of CT genotype % Continuous 23 Rate of TT genotype %... Continuous Rate of allele T % Continuous MTHFR gene at SNP rs1801133 Rate of CC genotype % Continuous Rate of CT genotype % Continuous 24 Rate of TT genotype % Continuous PCR machine Rate of allele... Continuous Rate of allele T % Continuous LRP5 gene at SNP rs41494349 Rate of CC genotype % Continuous Rate of CT genotype % Continuous 25 Rate of TT genotype % Continuous PCR machine Rate of allele