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新疆绝经 2 型糖尿病女性中 LRP5 基因 rs682429 和 rs3781590 多态性与突变与骨代谢的关系研究。

A Study of the Relationship between the Polymorphism and Mutation of rs682429 and rs3781590 in the LRP5 Gene and Bone Metabolism in Postmenopausal Type 2 Diabetic Women in Xinjiang.

机构信息

Department of Endocrinology and Metabolism, The First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang 832002, China.

Medical College, Shihezi University, Shihezi 832002, China.

出版信息

J Diabetes Res. 2020 Apr 28;2020:3071217. doi: 10.1155/2020/3071217. eCollection 2020.

DOI:10.1155/2020/3071217
PMID:32405501
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7204136/
Abstract

OBJECTIVE

To explore the expression of the polymorphism and mutation of rs682429 and rs3781590 in the low-density lipoprotein receptor-related protein 5 (LRP5) genotype and to analyse the relationship of bone mineral density (BMD) and bone metabolism markers in postmenopausal women with type-2 diabetes mellitus (T2DM) in Xinjiang, China, to provide a basis for prevention and treatment of the disease.

METHODS

A total of 136 postmenopausal women were included in the study. According to the results of an oral glucose tolerance test (OGTT) and dual-energy X-ray (DEXA) determination of BMD, the study subjects were divided into 4 groups: group A: normal OGTT+normal bone mass group; group B: normal OGTT+osteoporotic (OP) group; group C: T2DM+normal bone mass group; group D: T2DM+osteoporotic (OP) group. Calcium (Ca), phosphorus (P), alkaline phosphatase (ALP), and clinical biochemical data were determined; haemoglobin A1c (HbA1c) was measured by HPLC; BMD of the femoral neck, hip, and lumbar spine (L1-4) was measured by dual-energy X-ray (DEXA); and the rs682429 and rs3781590 polymorphisms of the LRP5 gene were detected by time-of-flight mass spectrometry (TOF MS).

RESULTS

(1) The rs682429 polymorphism of the LRP5 genotype distribution was statistically significant ( < 0.05) in group B compared with group A. (2) The triglycerides (TG) of women with the CT/TT genotype (mutant type) were higher than those of women with the CC genotype (wild type) (2.37 ± 1.30 vs. 1.52 ± 0.83, < 0.05) at the rs3781590 site of the LRP5 gene in group D. (3) Multiple linear regression analysis showed that TG ( = 0.034, < 0.05) and body mass index (BMI) ( = 0.013, < 0.05) were the influencing factors of BMD (L1-4) in T2DM patients. TG ( = 0.022, < 0.05), BMI ( = 0.009, < 0.05), and duration of menopause ( = 0.005, < 0.05) were the influencing factors of BMD (hip).

CONCLUSION

(1) The rs682429 polymorphism site in the LRP5 gene may be involved in bone metabolism in postmenopausal women from Xinjiang. (2) The rs3781590 mutation in the LRP5 gene from these subjects may be involved in lipid metabolism. (3) Among postmenopausal women with type 2 diabetes mellitus and bone mass abnormality in the Xinjiang Shihezi area, high BMI and TG are protective factors against increased BMD. Duration of menopause is a risk factor for increased BMD.

摘要

目的

探讨低密度脂蛋白受体相关蛋白 5(LRP5)基因 rs682429 和 rs3781590 多态性和突变在新疆绝经后 2 型糖尿病(T2DM)患者中的表达,分析其与骨密度(BMD)和骨代谢标志物的关系,为疾病的防治提供依据。

方法

选取新疆绝经后女性 136 例,根据口服葡萄糖耐量试验(OGTT)和双能 X 线(DEXA)测定的 BMD 结果,将研究对象分为 4 组:A 组:OGTT 正常+骨量正常组;B 组:OGTT 正常+骨质疏松(OP)组;C 组:T2DM+骨量正常组;D 组:T2DM+骨质疏松(OP)组。检测血钙(Ca)、血磷(P)、碱性磷酸酶(ALP)等临床生化指标;采用高效液相色谱法(HPLC)测定糖化血红蛋白 A1c(HbA1c);采用双能 X 线(DEXA)测定股骨颈、髋部和腰椎(L1-4)的 BMD;采用飞行时间质谱(TOF MS)法检测 LRP5 基因 rs682429 和 rs3781590 多态性。

结果

(1)B 组 LRP5 基因型 rs682429 多态性分布与 A 组比较差异有统计学意义( < 0.05)。(2)D 组 LRP5 基因 rs3781590 位点 CT/TT 基因型(突变型)女性的甘油三酯(TG)高于 CC 基因型(野生型)女性(2.37±1.30比 1.52±0.83, < 0.05)。(3)多元线性回归分析显示,TG( = 0.034, < 0.05)和体质指数(BMI)( = 0.013, < 0.05)是 T2DM 患者腰椎(L1-4)BMD 的影响因素。TG( = 0.022, < 0.05)、BMI( = 0.009, < 0.05)和绝经年限( = 0.005, < 0.05)是髋部 BMD 的影响因素。

结论

(1)LRP5 基因 rs682429 多态性可能与新疆绝经后女性的骨代谢有关。(2)LRP5 基因 rs3781590 突变可能与受试者的脂代谢有关。(3)在新疆石河子地区绝经后患有 2 型糖尿病和骨量异常的女性中,较高的 BMI 和 TG 是增加 BMD 的保护因素,绝经年限是增加 BMD 的危险因素。

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