The significance of polymorphisms and mutations in the LRP5 rs556442 and rs312778 locus genes in postmenopausal women with type 2 diabetes mellitus in the context of bone mass abnormalities
The significance of polymorphisms and mutations in the LRP5 rs556442 and rs312778 locus genes in postmenopausal women with type 2 diabetes mellitus in the context of bone mass abnormalities
黎娅 1李军 1李思源 2王曦龄 3卢韵秋 1李子昕1
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作者信息
1. 石河子大学第一附属医院,新疆石河子 832000
2. 石河子大学医学院,新疆石河子 832000
3. 湖南省娄底市中心医院,湖南娄底 417600
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摘要
目的 分析低密度脂蛋白受体相关蛋白 5(low density lipoprotein receptor related protein 5,LRP5)rs556442、rs312778 位点基因多态性及突变在绝经后女性2型糖尿病(type 2 diabetes mellitus,T2DM)患者中骨量异常的意义.方法 收集2021年5月至2023年5月新疆石河子地区的142例绝经后女性资料进行回顾性分析,分为正常对照组(A组,n=29)、T2DM组(B组,n=30)、骨量降低组(C组,n=28)、骨量降低+T2DM组(D组,n=55).收集记录相关基线资料,运用全自动生化测定仪测定受试者血糖、血脂及骨代谢指标.通过双能X线骨密度仪测定骨密度(bone mineral density BMD),LRP5基因位点多态性采用飞行时间质谱法(MALDI-TOF-MS)测定,采用SNPscan技术对上述SNP位点进行基因分型.结果 ①四组基线资料比较,绝经年限、年龄及腰臀比(waist hip ratio,WHR)比较差异具有统计学意义(P＜0.05);②与A组相比,B组的空腹血糖(FPG)、糖化血红蛋白(HbA1c)升高(P＜0.05);D组的FPG、HbA1c的血清学水平升高,甘油三酯(TG)血清学水平降低(P＜0.05);③rs556442位点:与A组相比,D组基因型分布(AA/AG/GG基因型)有统计学意义(P＜0.05);rs312778位点组间基因型(CC/CT/TT基因型)及等位基因分布频率均无统计学意义(P＞0.05);④rs556442位点:与AA基因型相比,B、C组AG/GG基因型的股骨颈BMD水平降低;D组AG/GG型的HDL血清学水平降低(P＜0.05).rs312778位点:与CC基因型相比,A组HbA1C、FPG血清学水平较CT/TT基因型低(P＜0.05);D组CT/TT基因型的低密度脂蛋白(LDL)血清学水平升高(P＜0.05);⑤多元线性回归分析:rs556442位点,TG增加是腰L,～4 BMD降低的危险因素(P＜0.05);rs312778位点,体质量指数(body mass index,BMI)降低是腰L1～4及股骨颈BMD降低的危险因素,TG增加是腰L1～4 BMD降低的危险因素(P＜0.05);⑥在rs556442、rs312778位点骨量异常与基因型分布均无统计学意义(P＞0.05).结论 新疆石河子地区绝经后T2DM女性患者LRP5基因rs556442、rs312778基因位点的突变可能与骨量降低有关.
Abstract
Objective To analyze the significance of polymorphisms and mutations at the rs556442 and rs312778 loci of low density lipoprotein receptor related protein 5 in the bone mass abnormalities of postmenopausal women with type 2 diabetes mellitus patients with abnormal bone mass.Methods The data of 142 postmenopausal women in Shihezi region of Xinjiang from May 2021 to May 2023 were collected and analyzed retrospectively;they were divided into four groups,namely,the normal control group(Group A,n=29),the T2DM group(Group B,n=30),the group with reduced bone mass(Group C,n=28),and the group with reduced bone mass+T2DM(Group D,n=55).Relevant baseline data were collected and recorded,and fully automated biochemical assay instrument was used to determine sugar,lipid and bone metabolism indexes.Bone mineral density was measured by dual-energy X-ray,and the polymorphism of LRP5 gene locus was determined by time-of-flight mass spectrometry.Results ①Compared with the baseline data of the four groups,there were statistically significant differences in menopausal years,age and waist-hip ratio(P＜0.05);② Compared with Group A,Group B had higher fasting blood glucose and glycosylated hemoglobin(P＜0.05);Group D had higher serological levels of FPG and HbA1c,and lower serological levels of TG(both P＜0.05);③At rs556442,there was a statistically significant difference in the distribution of genotypes in Group D compared with Group A(P＜0.05);there was no statistically significant difference in the distribution of genotypes and allele frequencies between groups at rs312778(P＞0.05);④The rs556442 locus:compared with the AA type,the BMD level of the femoral neck of the AG/GG type was lower in Groups B and C;the serological level of HDL of the AG/GG type was lower in Group D(P＜0.05).rs312778 locus:compared with the CC type,the serological level of HbA1C and FPG of Group A was lower than that of the CT/TT type(P＜0.05);the LDL serological level of Group D was lower than that of the CT/TT type(P＜0.05)of Group D had elevated serologic levels of LDL(P＜0.05);⑤ Multiple linear regression analysis:at rs556442,increased TG was a risk factor for decreased lumbar L1-4 BMD(P＜0.05);at rs312778,decreased BMI was a risk factor for decreased lumbar L1-4 and femoral neck BMD(P＜0.05),and increased TG was a risk factor for decreased lumbar L1-4 BMD;⑥There was no statistically significant association between bone mass abnormality and genotype distribution at the rs556442,locus(P＞0.05);at the rs312778 locus,there was a statistically significant association between bone mass abnormality and genotype distribution(P＜0.05).Conclusion Mutations in the rs556442 and rs312778 loci of the LRP5 gene in postmenopausal female patients with T2DM in the Shihezi region of Xinjiang may be associated with decreased bone mass.
关键词
低密度脂蛋白受体相关蛋白5/绝经女性/基因突变/骨量异常
Key words
low-density lipoprotein receptor-related protein 5/menopausal women/gene mutation/abnormal bone mass
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