Sun Xue, Zhang Rong, Jiang Feng, Tang Shanshan, Chen Miao, Peng Danfeng, Yan Jing, Wang Tao, Wang Shiyun, Bao Yuqian, Hu Cheng, Jia Weiping
Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
Shanghai Diabetes Institute, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China; Shanghai Jiao Tong University Affiliated Sixth People's Hospital South Campus, Shanghai, 201400, China.
PLoS One. 2015 Jan 24;10(1):e0116714. doi: 10.1371/journal.pone.0116714. eCollection 2015.
Elevated serum uric acid concentration is an independent risk factor and predictor of type 2 diabetes (T2D). Whether the uric acid-associated genes have an impact on T2D remains unclear. We aimed to investigate the effects of the uric acid-associated genes on the risk of T2D as well as glucose metabolism and insulin secretion.
We recruited 2,199 normal glucose tolerance subjects from the Shanghai Diabetes Study I and II and 2,999 T2D patients from the inpatient database of Shanghai Diabetes Institute. Fifteen single nucleotide polymorphisms (SNPs) mapped in or near 11 loci (PDZK1, GCKR, LRP2, SLC2A9, ABCG2, LRRC16A, SLC17A1, SLC17A3, SLC22A11, SLC22A12 and SF1) were genotyped and serum biochemical parameters related to uric acid and T2D were determined.
SF1 rs606458 showed strong association to T2D in both males and females (p = 0.034 and 0.0008). In the males, LRRC16A was associated with 2-h insulin and insulin secretion (p = 0.009 and 0.009). SLC22A11 was correlated with HOMA-B and insulin secretion (p = 0.048 and 0.029). SLC2A9 rs3775948 was associated with 2-h glucose (p = 0.043). In the females, LRP2 rs2544390 and rs1333049 showed correlations with fasting insulin, HOMA-IR and insulin secretion (p = 0.028, 0.033 and 0.052 and p = 0.034, 0.047 and 0.038, respectively). SLC2A9 rs11722228 was correlated with 2-h glucose, 2-h insulin and insulin secretion (p = 0.024, 0.049 and 0.049, respectively).
Our results indicated that the uric acid-associated genes have an impact on the risk of T2D, glucose metabolism and insulin secretion in a Chinese population.
血清尿酸浓度升高是2型糖尿病（T2D）的独立危险因素和预测指标。尿酸相关基因是否对T2D有影响尚不清楚。我们旨在研究尿酸相关基因对T2D风险以及糖代谢和胰岛素分泌的影响。
我们从上海糖尿病研究I和II中招募了2199名糖耐量正常的受试者，并从上海糖尿病研究所的住院数据库中招募了2999名T2D患者。对位于11个基因座（PDZK1、GCKR、LRP2、SLC2A9、ABCG2、LRRC16A、SLC17A1、SLC17A3、SLC22A11、SLC22A12和SF1）内或附近的15个单核苷酸多态性（SNP）进行基因分型，并测定与尿酸和T2D相关的血清生化参数。
SF1 rs606458在男性和女性中均与T2D有强关联（p = 0.034和0.0008）。在男性中，LRRC16A与2小时胰岛素及胰岛素分泌相关（p = 0.009和0.009）。SLC22A11与HOMA-B及胰岛素分泌相关（p = 0.048和0.029）。SLC2A9 rs3775948与2小时血糖相关（p = 0.043）。在女性中，LRP2 rs2544390和rs1333049与空腹胰岛素、HOMA-IR及胰岛素分泌相关（分别为p = 0.028、0.033和0.052以及p = 0.034、0.047和0.038）。SLC2A9 rs11722228与2小时血糖、2小时胰岛素及胰岛素分泌相关（分别为p = 0.024、0.049和0.049）。
我们的结果表明，尿酸相关基因对中国人群的T2D风险、糖代谢和胰岛素分泌有影响。
