Rojano-Mejía David, Coral-Vázquez Ramón M, Espinosa Leticia Cortes, López-Medina Guillermo, Aguirre-García María C, Coronel Agustín, Canto Patricia
División de Investigación Biomédica, Subdirección de Enseñanza e Investigación, Centro Médico Nacional 20 de Noviembre, Instituto de Seguridad y Servicios Sociales de los Trabajadores del Estado, San Lorenzo No. 502, 2nd piso. Col. del Valle, Delegación Benito Juárez, C.P. 03100, Mexico, D.F., Mexico.
Age (Dordr). 2013 Apr;35(2):471-8. doi: 10.1007/s11357-011-9363-9. Epub 2011 Dec 16.
Osteoporosis is characterized by low bone mineral density (BMD). One of the most important factors that influence BMD is the genetic contribution. The collagen type 1 alpha 1 (COL1A1) and the JAGGED (JAG1) have been investigated in relation to BMD. The aim of this study was to investigate the possible association between two single-nucleotide polymorphisms (SNPs) of COL1A1, their haplotypes, and one SNP of JAG1 with BMD in postmenopausal Mexican-Mestizo women. Seven hundred and fifty unrelated postmenopausal women were included. Risk factors were recorded and BMD was measured in lumbar spine, total hip, and femoral neck by dual-energy X-ray absorptiometry. DNA was obtained from blood leukocytes. Two SNPs in COL1A1 (rs1800012 and rs1107946) and one in JAG1 (rs2273061) were studied. Real-time PCR allelic discrimination was used for genotyping. The differences between the means of the BMDs according to genotype were analyzed with covariance. Deviations from Hardy-Weinberg equilibrium were tested. Pairwise linkage disequilibrium between single nucleotide polymorphisms was calculated by direct correlation r (2), and haplotype analysis of COL1A1 was conducted. Under a dominant model, the rs1800012 polymorphism of the COL1A1 showed an association with BMD of the lumbar spine (P = 0.021). In addition, analysis of the haplotype of COL1A1 showed that the G-G haplotype presented a higher BMD in lumbar spine. We did not find an association between the s1107946 and rs2273061 polymorphisms of the COL1A1 and JAG1, respectively. Our results suggest that the rs1800012 polymorphism of the COL1A1, in addition to one haplotype, were significantly associated with BMD variation in Mexican-Mestizo postmenopausal women.
骨质疏松症的特征是骨矿物质密度（BMD）低。影响骨矿物质密度的最重要因素之一是遗传因素。已经对1型胶原蛋白α1（COL1A1）和锯齿蛋白（JAG1）与骨矿物质密度的关系进行了研究。本研究的目的是调查绝经后墨西哥梅斯蒂索妇女中COL1A1的两个单核苷酸多态性（SNP）、它们的单倍型以及JAG1的一个SNP与骨矿物质密度之间可能存在的关联。纳入了750名无亲属关系的绝经后妇女。记录危险因素，并通过双能X线吸收法测量腰椎、全髋和股骨颈的骨矿物质密度。从血液白细胞中提取DNA。研究了COL1A1中的两个SNP（rs1800012和rs1107946）以及JAG1中的一个SNP（rs2273061）。采用实时荧光定量PCR等位基因分型法进行基因分型。用协方差分析根据基因型划分的骨矿物质密度均值之间的差异。检验是否偏离哈迪-温伯格平衡。通过直接相关系数r（2）计算单核苷酸多态性之间的成对连锁不平衡，并对COL1A1进行单倍型分析。在显性模型下，COL1A1的rs1800012多态性与腰椎骨矿物质密度相关（P = 0.021）。此外，COL1A1单倍型分析表明，G-G单倍型在腰椎呈现出更高的骨矿物质密度。我们分别未发现COL1A1的s1107946和JAG1的rs2273061多态性之间存在关联。我们的结果表明，COL1A1的rs1800012多态性以及一种单倍型与墨西哥梅斯蒂索绝经后妇女的骨矿物质密度变化显著相关。
