ATP结合盒家族G蛋白亚家族2单核苷酸多态性与高尿酸血症的关系

The associations between adenosine triphosphate binding cassette subfamily G member-2 single nucleotide polymorphism and hyperuricemia in a Chinese tertiary hospital faculty cohort

目的 研究在不同年龄、性别中ATP结合盒家族G蛋白亚家族2（ABCG2）单核苷酸多态性rs2231142（C〉A）与高尿酸血症的相关性.方法 选北京协和医院职工体检人群为研究对象,男性血尿酸〉416.4μmol/L、女性血尿酸〉359.6μmol/L者纳入高尿酸血症组,另选血尿酸水平正常者为对照组.采用扩增耐突变系统-聚合酶链反应检测ABCG2基因型,分析ABCG2 rs2231142与高尿酸血症的相关性,以及基因与性别的交互作用.结果 高尿酸血症组ABCG2 rs2231142A等位基因频率高于对照组（38.38%比26.62%,P〈0.001）,OR=2.89（95%CI 1.91-4.37,P〈0.001）,调整高血压、高血糖、高血脂后,OR=2.99（95%CI 1.94-4.62,P〈0.001）.亚组分析显示,男性高尿酸血症的相对风险高于女性,OR值分别为3.83（95%CI 2.03-7.24,P〈0.001）、2.30（95%CI 1.32-4.00,P=0.003）.年龄≥55岁者,男性和女性ABCG2 rs2231142 A等位基因携带者发生高尿酸血症的相对风险相仿;而年龄〈55岁者,男性ABCG2 rs2231142 A等位基因携带者发生高尿酸血症的相对风险高于女性,OR值分别为4.11（95%CI 1.92-8.79,P〈0.001）、1.73（95%CI 0.80-3.76,P=0.165）,交互性分析未达统计学意义.结论 我院职工体检人群中,ABCG2 rs2231142 A等位基因是发生高尿酸血症的独立危险因素.

Objective To investigate gender specific association between single nucleotide polymorphism rs2231142 and hyperuricemia .Method A matched case-control study was conducted in a faculty cohort of a tertiary hospital in Beijing .The enrollment criteria were faculty member of the hospital with signed consent .The exclusion criteria were tumor , previous renal diseases , renal function damage , pregnancy , currently taking medicines that could increase or decrease serum uric acid level , and those who had gout.Males with serum uric acid 〉416.4 μmol/L and females with serum uric acid 〉359.6 μmol/L were enrolled as hyperuricemia group .Subjects with normal serum uric acid were randomly enrolled at 1：2 ratio after matching for gender , age, renal function and body mass index .Rs2231142（ C〉A） was assayed by amplification refractory mutation system polymerase chain reaction , with common forward primer：5′GGCTTTGCAGACATCTATGG 3′, C specific reverse primer：5′CGAAGAGCTGCTGAGAAATG 3′, and A specific reverse primer：5′CGAAGAGCTGCTGAGAAATT 3′.Association between rs 2231142 and hyperuricemia was analyzed in the general study group , as well as different gender and age groups .Results A total of 198 subjects with hyperuricemia and 370 controls were enrolled .The A allele frequency of rs2231142 was significantly higher in the hyperuricemia group than control group （38.38% vs 26.62%, P〈0.001）, with an OR for hyperuricemia of 2.89 （95%CI 1.91-4.37, P〈0.001）.After adjustment for hypertension, hyperglycemia and dyslipidemia , the OR was 2.99 （95%CI 1.94 -4.62, P〈0.001）. Subgroup analysis showed that the ORs were 3.83 （95%CI 2.03-7.24, P〈0.001） in male and 2.30 （95%CI 1.32-4.00, P=0.003） in female.In those 55 years or older, the gender differences of ORs were decreased, with ORs of 3.23 （95%CI 1.02-10.29, P=0.047） in male and 3.06 （95%CI 1.37-6.84, P=0.006） in female.While in those less than 55 years, the gender differences of ORs were enlarged, with ORs of 4.11 （95%CI 1.92-8.79, P〈0.001） in males and 1.73 （95%CI 0.80-3.76, P=0.165） in females.Interaction study between gender and rs 2231142 did not reach significant level in both the gender group and two age groups . Conclusion Single nucleotide polymorphism rs 2231142 A allele is an independent risk factor for hyperuricemia in this tertiary hospital faculty cohort .The ORs are higher in male than those in female , especially in those less than 55 years old .