CAJ | 학술논문

目的探讨葡萄糖转运体9（SLC2A9）基因 rs3733591（C>T）的单核苷酸多态性（SNPs）与我国汉族人群痛风发病及血尿酸水平的相关性，并分析其多态性与痛风患者、健康体检者 PBMCs SLC2A9 mRNA 表达的相关性。方法①采用 TaqMan?探针法检测痛风组（297例原发性痛风性关节炎患者）和健康对照组（211名健康体检者） rs3733591（C>T）位点的基因型，χ2检验比较2组基因型及等位基因分布频率，计算比值比（OR）及95%可信区间（95%CI）。②采用实时荧光定量-PCR（RT-qPCR）法检测46例间歇期痛风患者及40名健康对照组 PBMCs SLC2A9 mRNA 的表达水平，非参数检验比较各组变量间的差异，并分析与 rs3733591（C>T）多态性的相关性。结果 rs3733591（C>T）位点的 TT 基因型在痛风组的分布频率显著低于健康对照组（37.7%与48.3%，P=0.017），携带 TT 基因型的个体罹患痛风的相对风险OR 为0.647（95%CI：0.452~0.925）。而等位基因 T 在痛风组中的分布频率为60.9%，显著低于健康对照组的69.2%（χ2=7.324，P=0.007），携带等位基因 T 的个体罹患痛风的相对风险 OR 为0.695（95%CI：0.533~0.905）；等位基因 C 在痛风组中的分布频率为39.1%，显著高于健康对照组的30.8%（χ2=1.440，P<0.05）。痛风组中携带 TC 基因型个体的外周血单个核细胞 SLC2A9 mRNA 的表达水平显著高于携带 TT 基因型者，而痛风组及健康对照组携带其他基因型的个体 SLC2A9 mRNA 的表达差异无统计学意义（P>0.05）。有痛风石（30例）痛风患者与无痛风石（190例）痛风患者的基因型及等位基因分布频率差异无统计学意义（P>0.05）。结论本研究提示 SLC2A9基因 rs3733591（C>T）位点的多态性可能与我国汉族人群原发性痛风的易感性相关，而与痛风患者痛风石形成无关；等位基因 C 可能为痛风发病的风险因子，而 TT 基因型及 T 等位基因可能对痛风发病具有保护作用；其多态性可能通过影响 SLC2A9基因的转录表达水平来参与痛风的发病。目的探討葡萄糖轉運體9（SLC2A9）基因 rs3733591（C>T）的單覈苷痠多態性（SNPs）與我國漢族人群痛風髮病及血尿痠水平的相關性，併分析其多態性與痛風患者、健康體檢者 PBMCs SLC2A9 mRNA 錶達的相關性。方法①採用 TaqMan?探針法檢測痛風組（297例原髮性痛風性關節炎患者）和健康對照組（211名健康體檢者） rs3733591（C>T）位點的基因型，χ2檢驗比較2組基因型及等位基因分佈頻率，計算比值比（OR）及95%可信區間（95%CI）。②採用實時熒光定量-PCR（RT-qPCR）法檢測46例間歇期痛風患者及40名健康對照組 PBMCs SLC2A9 mRNA 的錶達水平，非參數檢驗比較各組變量間的差異，併分析與 rs3733591（C>T）多態性的相關性。結果 rs3733591（C>T）位點的 TT 基因型在痛風組的分佈頻率顯著低于健康對照組（37.7%與48.3%，P=0.017），攜帶 TT 基因型的箇體罹患痛風的相對風險OR 為0.647（95%CI：0.452~0.925）。而等位基因 T 在痛風組中的分佈頻率為60.9%，顯著低于健康對照組的69.2%（χ2=7.324，P=0.007），攜帶等位基因 T 的箇體罹患痛風的相對風險 OR 為0.695（95%CI：0.533~0.905）；等位基因 C 在痛風組中的分佈頻率為39.1%，顯著高于健康對照組的30.8%（χ2=1.440，P<0.05）。痛風組中攜帶 TC 基因型箇體的外週血單箇覈細胞 SLC2A9 mRNA 的錶達水平顯著高于攜帶 TT 基因型者，而痛風組及健康對照組攜帶其他基因型的箇體 SLC2A9 mRNA 的錶達差異無統計學意義（P>0.05）。有痛風石（30例）痛風患者與無痛風石（190例）痛風患者的基因型及等位基因分佈頻率差異無統計學意義（P>0.05）。結論本研究提示 SLC2A9基因 rs3733591（C>T）位點的多態性可能與我國漢族人群原髮性痛風的易感性相關，而與痛風患者痛風石形成無關；等位基因 C 可能為痛風髮病的風險因子，而 TT 基因型及 T 等位基因可能對痛風髮病具有保護作用；其多態性可能通過影響 SLC2A9基因的轉錄錶達水平來參與痛風的髮病。
목적탐토포도당전운체9（SLC2A9）기인 rs3733591（C>T）적단핵감산다태성（SNPs）여아국한족인군통풍발병급혈뇨산수평적상관성，병분석기다태성여통풍환자、건강체검자 PBMCs SLC2A9 mRNA 표체적상관성。방법①채용 TaqMan?탐침법검측통풍조（297례원발성통풍성관절염환자）화건강대조조（211명건강체검자） rs3733591（C>T）위점적기인형，χ2검험비교2조기인형급등위기인분포빈솔，계산비치비（OR）급95%가신구간（95%CI）。②채용실시형광정량-PCR（RT-qPCR）법검측46례간헐기통풍환자급40명건강대조조 PBMCs SLC2A9 mRNA 적표체수평，비삼수검험비교각조변량간적차이，병분석여 rs3733591（C>T）다태성적상관성。결과 rs3733591（C>T）위점적 TT 기인형재통풍조적분포빈솔현저저우건강대조조（37.7%여48.3%，P=0.017），휴대 TT 기인형적개체리환통풍적상대풍험OR 위0.647（95%CI：0.452~0.925）。이등위기인 T 재통풍조중적분포빈솔위60.9%，현저저우건강대조조적69.2%（χ2=7.324，P=0.007），휴대등위기인 T 적개체리환통풍적상대풍험 OR 위0.695（95%CI：0.533~0.905）；등위기인 C 재통풍조중적분포빈솔위39.1%，현저고우건강대조조적30.8%（χ2=1.440，P<0.05）。통풍조중휴대 TC 기인형개체적외주혈단개핵세포 SLC2A9 mRNA 적표체수평현저고우휴대 TT 기인형자，이통풍조급건강대조조휴대기타기인형적개체 SLC2A9 mRNA 적표체차이무통계학의의（P>0.05）。유통풍석（30례）통풍환자여무통풍석（190례）통풍환자적기인형급등위기인분포빈솔차이무통계학의의（P>0.05）。결론본연구제시 SLC2A9기인 rs3733591（C>T）위점적다태성가능여아국한족인군원발성통풍적역감성상관，이여통풍환자통풍석형성무관；등위기인 C 가능위통풍발병적풍험인자，이 TT 기인형급 T 등위기인가능대통풍발병구유보호작용；기다태성가능통과영향 SLC2A9기인적전록표체수평래삼여통풍적발병。
Objective To investigate the single nucleotide polymorphisms(SNPs) rs3733591(C>T) of SLC2A9 gene in Chinese Han population, and to explore the association of this gene polymorphisms with gout susceptibility, tophi, serum uric acid levels, other clinical and laboratory data and the levels of SLC2A9 mRNA of peripheral blood mononuclear cells(PBMCs). Methods ① A total of 297 primary gout arthritis patients(GA) and 211 normal controls(NC) were enrolled into this study. The clinical and laboratory data of patients were collected. The genotypes and alleles frequencies were measured by using TaqMan ?SNP Geno-typing Assays and the possible association between gene polymorphism of SLC2A9 and gout was investigated by Chi-square test. The odds ratios(OR) and 95% confidence intervals(95%CI) were calculated. ② The lev-els of SLC2A9 mRNA on PBMCs of 86 gout patients(46 patients in remission) and controls were measured by real-time quantitative polymerase chain reaction (RT-qPCR). The nonparametric test was used to analyze the expression in different groups. Results The frequencies of genotypes and alleles of rs3733591(C>T) in gout patients were different from controls(P<0.05). The frequency of TT genotype was significantly lower than that in controls (P<0.05) and the relative risk of this genotype to develop gout was 0.647 (95%CI: 0.452-0.925). Moreover, the frequency of T allele in cases was much lower than in controls (60.9% vs 69.2%, χ2=7.324, P=0.007, OR=0.695), but the frequency of C allele was much higher(39.1% vs 30.8%, χ2=1.440, P=0.007, OR=1.440). Interestingly, the levels of SLC2A9 mRNA on PBMCs in gout patients who carried TC genotype of rs3733591 was higher than those who carried TT genotype(P<0.05). There was no difference in the expression of SLC2A9 mRNA on PBMCs among different genotype carriers of rs3733591 in controls (P>0.05). However, there was no significant difference in the distribution of genotypes and alleles between 30 tophaceous gout patients and 190 non-tophaceous gout patients(P>0.05). Conclusion Results of present study suggest the rs3733591(C>T) polymorphism of the SLC2A9 gene might be associated with gout development, but not with tophaceous gout. The C allele predisposes to gout, and TT genotype and T allele might protect Chinese Han population from developing gout. The rs3733591(C>T) polymorphism probably affects the susceptibility to gout by influencing the f expression of SLC2A9 mRNA susceptibility.