Wang Ke-Sheng, Wang Liang, Liu Xuefeng, Zeng Min
Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, P.O. Box 70259, Lamb Hall, Johnson City, TN 37614-1700, USA.
J Genet. 2013 Dec;92(3):395-402. doi: 10.1007/s12041-013-0279-2.
The heparan sulfate 6-O-sulfotransferase 3 (HS6ST3) gene is involved in heparan sulphate and heparin metabolism, and has been reported to be associated with diabetic retinopathy in type 2 diabetes.We hypothesized that HS6ST3 gene polymorphisms might play an important role in obesity and related phenotypes (such as triglycerides). We examined genetic associations of 117 single-nucleotide polymorphisms (SNPs) within the HS6ST3 gene with obesity and triglycerides using two Caucasian samples: the Marshfield sample (1442 obesity cases and 2122 controls), and the Health aging and body composition (Health ABC) sample (305 cases and 1336 controls). Logistic regression analysis of obesity as a binary trait and linear regression analysis of triglycerides as a continuous trait, adjusted for age and sex, were performed using PLINK. Single marker analysis showed that six SNPs in the Marshfield sample and one SNP in the Health ABC sample were associated with obesity (P < 0.05). SNP rs535812 revealed a stronger association with obesity in meta-analysis of these two samples (P = 0.0105). The T-A haplotype from rs878950 and rs9525149 revealed significant association with obesity in the Marshfield sample (P = 0.012). Moreover, nine SNPs showed associations with triglycerides in the Marshfield sample (P < 0.05) and the best signal was rs1927796 (P = 0.00858). In addition, rs7331762 showed a strong gene x gender interaction (P = 0.00956) for obesity while rs1927796 showed a strong gene x gender interaction (P = 0.000625) for triglycerides in the Marshfield sample. These findings contribute new insights into the pathogenesis of obesity and triglycerides and demonstrate the importance of gender differences in the aetiology.
硫酸乙酰肝素6 - O -磺基转移酶3（HS6ST3）基因参与硫酸乙酰肝素和肝素的代谢，据报道其与2型糖尿病的糖尿病视网膜病变有关。我们推测HS6ST3基因多态性可能在肥胖及相关表型（如甘油三酯）中起重要作用。我们使用两个白种人样本研究了HS6ST3基因内117个单核苷酸多态性（SNP）与肥胖和甘油三酯的遗传关联：马什菲尔德样本（1442例肥胖病例和2122例对照）以及健康老龄化与身体成分（Health ABC）样本（305例病例和1336例对照）。使用PLINK对作为二元性状的肥胖进行逻辑回归分析，对作为连续性状的甘油三酯进行线性回归分析，并对年龄和性别进行了校正。单标记分析表明，马什菲尔德样本中的6个SNP和Health ABC样本中的1个SNP与肥胖相关（P < 0.05）。SNP rs535812在这两个样本的荟萃分析中显示出与肥胖更强的关联（P = 0.0105）。rs878950和rs9525149的T - A单倍型在马什菲尔德样本中显示出与肥胖显著相关（P = 0.012）。此外，9个SNP在马什菲尔德样本中显示出与甘油三酯相关（P < 0.05），最佳信号是rs1927796（P = 0.00858）。此外，在马什菲尔德样本中，rs7331762对肥胖显示出强烈的基因×性别相互作用（P = 0.00956），而rs1927796对甘油三酯显示出强烈的基因×性别相互作用（P = 0.000625）。这些发现为肥胖和甘油三酯的发病机制提供了新的见解，并证明了性别差异在病因学中的重要性。
