Canales Benjamin K, Smith Jennifer A, Weiner I David, Ware Erin B, Zhao Wei, Kardia Sharon L R, Curhan Gary C, Turner Stephen T, Perinpam Majuran, Lieske John C
Department of Urology, University of Florida College of Medicine, Gainesville, Florida, USA.
Urology Service, Gainesville VA Medical Center, Gainesville, Florida, USA.
Kidney Int Rep. 2017 Jun 21;2(6):1111-1121. doi: 10.1016/j.ekir.2017.06.009. eCollection 2017 Nov.
Urine pH is critical for net acid and solute excretion, but the genetic factors that contribute to its regulation are incompletely understood.
We tested the association of single nucleotide polymorphisms (SNPs) from 16 genes related to ammonia (NH) metabolism (15 biological candidates selected , 1 selected from a previous genome-wide association study analysis) to that of 24-hour urine pH in 2493 individuals of European descent across 2 different cohorts using linear regression, adjusting for age, sex, and body mass index.
Of 2871 total SNPs in these genes, 13 SNPs in (a4 subunit of hydrogen- adenosine triphosphatase), (sodium/hydrogen exchanger, isoform 3), and (Rhesus C glycoprotein), and 12 SNPs from insulin-like growth factor binding protein 7 () had a meta-analysis value <0.01 in the joint analysis plus a consistent direction of effect and at a least suggestive association ( < 0.1) in both cohorts. The maximal effect size (in pH units) for each additional minor allele of the identified SNPs was -0.13 for , -0.08 for , 0.06 for , and -0.06 for ; SNP rs34447434 in had the lowest meta-analysis value ( = 7.1 × 10). After adjusting for net alkali absorption, urine pH remained suggestively associated with multiple SNPs in , 1 SNP in , and a new SNP in (phosphate-dependent glutaminase).
Overall, these findings suggest that variants in common genes involved in ammonia metabolism may substantively contribute to basal urine pH regulation. These variations might influence the likelihood of developing disease conditions associated with altered urine pH, such as uric acid or calcium phosphate kidney stones.
尿液pH值对于净酸和溶质排泄至关重要，但对其调节作用的遗传因素尚不完全清楚。
我们使用线性回归，对来自2个不同队列的2493名欧洲裔个体中与氨（NH）代谢相关的16个基因（选择了15个生物学候选基因，1个选自先前的全基因组关联研究分析）的单核苷酸多态性（SNP）与24小时尿液pH值之间的关联进行了测试，并对年龄、性别和体重指数进行了校正。
在这些基因的2871个SNP中，ATP6V1B1（氢 - 腺苷三磷酸酶的a4亚基）、SLC9A3（钠/氢交换体，异构体3）和RHCG（恒河猴C糖蛋白）中的13个SNP，以及胰岛素样生长因子结合蛋白7（IGFBP7）中的12个SNP在联合分析中的荟萃分析P值<0.01，且效应方向一致，并且在两个队列中至少有提示性关联（P < 0.1）。所鉴定SNP的每个额外次要等位基因的最大效应大小（以pH单位计），ATP6V1B1为-0.13，SLC9A3为-0.08，RHCG为0.06，IGFBP7为-0.06；IGFBP7中的SNP rs34447434的荟萃分析P值最低（P = 7.1×10）。在校正净碱吸收后，尿液pH值仍与ATP6V1B1中的多个SNP、SLC9A3中的1个SNP以及PAGln（磷酸依赖性谷氨酰胺酶）中的1个新SNP存在提示性关联。
总体而言，这些发现表明参与氨代谢的常见基因中的变异可能对基础尿液pH调节有实质性贡献。这些变异可能会影响发生与尿液pH改变相关疾病的可能性，如尿酸或磷酸钙肾结石。
