Genetic Heterogeneity of Kidney Stone Disease in Northeastern Thai Patients
Keywords:
Kidney stone disease; single nucleotide polymorphism; exome sequencing; genetic heterogeneity; Northeast ThailandAbstract
Kidney stone disease (KSD) is a health problem worldwide, with a reportedly increasing prevalence and incidence across the world. In Thailand, KSD is common in the north (N) and northeastern (NE) parts of the country, with the NE region accounting for more than 40% of total patients. Calcium stones comprise 80% of all kidney stones, making them the most prevalent globally, and also in Thailand. Generally, KSD is often associated with metabolic abnormalities of the urinary solute concentration or decreased urinary solubility, including hypercalciuria, hyperoxaluria, hypocitraturia, hyperuricosuria, cystinuria, low urinary volume, and defects in urinary acidification. The etiology of KSD is poorly understood but it is known that both genetic and environmental factors are involved and the disease is heterogeneous, ranging from monogenic defects to complex interactions between genetic and environmental factors. The reported studies of KSD using genetic and genomic approaches have revealed that ion transporters and channels, the calcium-sensing receptor signaling pathway, and the metabolic pathways of vitamin D, oxalate, cysteine, purines, and uric acid play important roles in causing KSD. In Thailand, studies of KSD employing different genetic and genomic approaches i.e. candidate gene analysis, genome-wide association studies (GWAS), linkage analysis, and next-generation sequencing, have identified genetic alterations in F2, PAQR6, SLC13A2, ITLN1, SCN10A, and PBK genes. These have provided insights into both the common and rare genetic variants and genetic heterogeneity of KSD in Thai patients. The identification of genetic defects and molecular pathways causing KSD in the Thai cohort contribute to the increase of our understanding of the pathogenesis of KSD.
References
Abe Y, Matsumoto S, Kito K, Ueda N. Cloning and expression of a novel MAPKK-like protein kinase, lymphokine-activated killer T-cell-originated protein kinase, specifically expressed in the testis and activated lymphoid cells. J Biol Chem. 2000; 275(28): 21525-21531.
Aegukkatajit S, Nagaphant A, Nuhung R, Sinturat R, Nugoonsawat P, Mungmai P. Epidemiological study of urinary stones based on operative theater data at regional hospitals and general hospitals of public health region-5, Thailand. J Med Assoc Thai. 1994; 77(9): 484-487.
Aggarwal KP, Narula S, Kakkar M, Tandon C. Nephrolithiasis: molecular mechanism of renal stone formation and the critical role played by modulators. Biomed Res Int. 2013; 2013: 292953.
Allison MJ, Cook HM, Milne DB, Gallagher S, Clayman RV. Oxalate degradation by gastrointestinal bacteria from humans. J Nutr. 1986; 116(3): 455-460.
Ayllon V, O'Connor R. PBK/TOPK promotes tumour cell proliferation through p38 MAPK activity and regulation of the DNA damage response. Oncogene. 2007; 26(24): 3451-3461.
Beck BB, Baasner A, Buescher A, Habbig S, Reintjes N, Kemper M J, Sikora P, Mache C, Pohl M, Stahl M, et al. Novel findings in patients with primary hyperoxaluria type III and implications for advanced molecular testing strategies. Eur J Hum Genet. 2013; 21(2): 162-172.
Bid HK, Kumar A, Kapoor R, Mittal RD. Association of Vitamin D Receptor-Gene (FokI) Polymorphism with Calcium Oxalate Nephrolithiasis. J Endourol. 2005; 19(1): 111-115.
Bigelow MW, Wiessner JH, Kleinman JG, Mandel NS. Calcium oxalate-crystal membrane interactions: dependence on membrane lipid composition. J Urol. 1996; 155(3): 1094-1098.
Bodmer W, Bonilla C. Common and rare variants in multifactorial susceptibility to common diseases. Nat Genet. 2008; 40(6): 695-701.
Botstein D, Risch N. Discovering genotypes underlying human phenotypes: past successes for mendelian disease, future approaches for complex disease. Nat Genet. 2003; 33 Suppl: 228-237.
Braun DA, Lawson JA, Gee HY, Halbritter J, Shril S, Tan W, Stein D, Wassner AJ, Ferguson MA, Gucev Z, et al. Prevalence of monogenic causes in pediatric patients with nephrolithiasis or nephrocalcinosis. Clin J Am Soc Nephrol. 2016; 11(4): 664-672.
Brunette MG, Leclerc M. Renal action of progesterone: effect on calcium reabsorption. Mol Cell Endocrinol. 2002; 194(1-2): 183-190.
Cellini B, Oppici E, Paiardini A, Montioli R. Molecular insights into primary hyperoxaluria type 1 pathogenesis. Front Biosci (Landmark Ed). 2012; 17: 621-634.
Chambers JC, Zhao J, Terracciano CM, Bezzina CR, Zhang W, Kaba R, Navaratnarajah M, Lotlikar A, Sehmi JS, Kooner MK, et al. Genetic variation in SCN10A influences cardiac conduction. Nat Genet. 2010; 42(2): 149-152.
Chow K, Dixon J, Gilpin S, Kavanagh J P, Rao PN. Citrate inhibits growth of residual fragments in an in vitro model of calcium oxalate renal stones. Kidney Int. 2004; 65(5): 1724-1730.
Coe FL, Evan A, Worcester E. Kidney stone disease. J Clin Invest. 2005; 115(10): 2598-2608.
Coe FL, Parks JH, Moore ES. Familial idiopathic hypercalciuria. N Engl J Med. 1979; 300(7): 337-340.
Cupisti A, Farnesi I, Armillotta N, Francesca F. Staghorn cystine stone in a 72-year-old recurrent calcium stone former. Clin Nephrol. 2012; 78(1): 76-80.
Daga A, Majmundar AJ, Braun DA, Gee HY, Lawson JA, Shril S, Jobst-Schwan T, Vivante A, Schapiro D, Tan W, et al. Whole exome sequencing frequently detects a monogenic cause in early onset nephrolithiasis and nephrocalcinosis. Kidney Int. 2018; 93(1): 204-213.
Danpure CJ, Rumsby G. Molecular aetiology of primary hyperoxaluria and its implications for clinical management. Expert Rev Mol Med. 2004; 6(1): 1-16.
Dawn Teare M, Barrett J H. Genetic linkage studies. Lancet. 2005; 366(9490): 1036-1044.
Ding Q, Fan B, Shi Y, Fan Z, Ding L, Li F, Tu W, Jin X, Qin C, Cao Q. Calcium-sensing receptor genetic polymorphisms and risk of developing nephrolithiasis in a Chinese population. Urol Int. 2017; 99(3): 331-337.
Dressing GE, Thomas P. Identification of membrane progestin receptors in human breast cancer cell lines and biopsies and their potential involvement in breast cancer. Steroids. 2007; 72(2): 111-116.
Evan AP, Coe FL, Lingeman JE, Worcester E. Insights on the pathology of kidney stone formation. Urol Res. 2005; 33(5): 383-389.
Farber CR, Lusis AJ. Future of osteoporosis genetics: enhancing genome-wide association studies. J Bone Miner Res. 2009; 24(12): 1937-1942.
Fernandes MS, Pierron V, Michalovich D, Astle S, Thornton S, Peltoketo H, Lam EW, Gellersen B, Huhtaniemi I, Allen J, et al. Regulated expression of putative membrane progestin receptor homologues in human endometrium and gestational tissues. J Endocrinol. 2005; 187(1): 89-101.
Gambaro G, Vezzoli G, Casari G, Rampoldi L, D’Angelo A, Borghi L. Genetics of hypercalciuria and calcium nephrolithiasis: From the rare monogenic to the common polygenic forms. Am J Kidney Dis. 2004; 44(6): 963-986.
Gao B, Yasui T, Itoh Y, Li Z, Okada A, Tozawa K, Hayashi Y, Kohri K. Association of osteopontin gene haplotypes with nephrolithiasis. Kidney Int. 2007a; 72(5): 592-598.
Gao B, Yasui T, Itoh Y, Tozawa K, Hayashi Y, Kohri K. A polymorphism of matrix Gla protein gene is associated with kidney stones. J Urol. 2007b; 177(6): 2361-2365.
Garrison SR, Weyer AD, Barabas ME, Beutler BA, Stucky CL. A gain-of-function voltage-gated sodium channel 1.8 mutation drives intense hyperexcitability of A- and C-fiber neurons. Pain. 2014; 155(5): 896-905.
Gaudet S, Branton D, Lue R A. Characterization of PDZ-binding kinase, a mitotic kinase. Proc Natl Acad Sci U S A. 2000; 97(10): 5167-5172.
Gilissen C, Hoischen A, Brunner H G, Veltman J A. Unlocking Mendelian disease using exome sequencing. Genome Biol. 2011; 12(9): 228.
Goldfarb DS, Fischer ME, Keich Y, Goldberg J. A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int. 2005; 67(3): 1053-1061.
Griffin DG. A review of the heritability of idiopathic nephrolithiasis. J Clin Pathol. 2004; 57(8): 793-796.
Halbritter J. Genetics of kidney stone disease-Polygenic meets monogenic. Nephrol Ther. 2021; 17S: S88-S94.
Halbritter J, Baum M, Hynes AM, Rice SJ, Thwaites DT, Gucev ZS, Fisher B, Spaneas L, Porath JD, Braun DA, et al. Fourteen monogenic genes account for 15% of nephrolithiasis/nephrocalcinosis. J Am Soc Nephrol. 2015; 26(3): 543-551.
Hoopes RR, Jr., Shrimpton AE, Knohl SJ, Hueber P, Hoppe B, Matyus J, Simckes A, Tasic V, Toenshoff B, Suchy S F, et al. Dent Disease with mutations in OCRL1. Am J Hum Genet. 2005; 76(2): 260-267.
Howles SA, Wiberg A, Goldsworthy M, Bayliss AL, Gluck AK, Ng M, Grout E, Tanikawa C, Kamatani Y, Terao C, et al. Genetic variants of calcium and vitamin D metabolism in kidney stone disease. Nat Commun. 2019; 10(1): 5175.
Hu D, Barajas-Martinez H, Pfeiffer R, Dezi F, Pfeiffer J, Buch T, Betzenhauser MJ, Belardinelli L, Kahlig KM, Rajamani S, et al. Mutations in SCN10A are responsible for a large fraction of cases of Brugada syndrome. J Am Coll Cardiol. 2014; 64(1): 66-79.
Johnson CM, Wilson DM, O'Fallon WM, Malek RS, Kurland LT. Renal stone epidemiology: a 25-year study in Rochester, Minnesota. Kidney Int. 1979; 16(5): 624-631.
Khan SR. Reactive oxygen species as the molecular modulators of calcium oxalate kidney stone formation: evidence from clinical and experimental investigations. J Urol. 2013; 189(3): 803-811.
Khaskhali MH, Byer K J, Khan S R. The effect of calcium on calcium oxalate monohydrate crystal-induced renal epithelial injury. Urol Res. 2009; 37(1): 1-6.
Koyuncu HH, Yencilek F, Eryildirim B, Sarica K. Family history in stone disease: how important is it for the onset of the disease and the incidence of recurrence? Urol Res. 2010; 38(2): 105-109.
Lai KC, Lin WY, Man KM, Tsai CH, Chen HY, Tsai FJ, Chen FJ, Chen HY, Liu HP, Ho TJ. Association of interleukin-18 gene polymorphisms with calcium oxalate kidney stone disease. Scand J Urol Nephrol. 2010; 44(1): 20-26.
Li H, Zhang J, Long J, Shi J, Luo Y. Calcium‐sensing receptor gene polymorphism (rs7652589) is associated with calcium nephrolithiasis in the population of Yi nationality in Southwestern China. Ann Hum Genet. 2018a; 82(5): 265-271.
Li X, Dang X, Cheng Y, Zhang D, Zhang X, Zou T, Xing J. Common variants in ALPL gene contribute to the risk of kidney stones in the Han Chinese population. Genet Test Mol Biomarkers. 2018b; 22(3): 187-192.
Lieske JC, Deganello S, Toback F G. Cell-crystal interactions and kidney stone formation. Nephron. 1999; 81 Suppl 1: 8-17.
Lieske JC, Rule AD, Krambeck AE, Williams JC, Bergstralh EJ, Mehta RA, Moyer TP. Stone composition as a function of age and sex. Clin J Am Soc Nephrol. 2014; 9(12): 2141-2146.
Loredo-Osti JC, Roslin NM, Tessier J, Fujiwara TM, Morgan K, Bonnardeaux A. Segregation of urine calcium excretion in families ascertained for nephrolithiasis: evidence for a major gene. Kidney Int. 2005; 68(3): 966-971.
Lu X, Sun D, Xu B, Pan J, Wei Y, Mao X, Yu D, Liu H, Gao B. In silico screening and molecular dynamic study of nonsynonymous single nucleotide polymorphisms associated with kidney stones in the SLC26A6 gene. J Urol. 2016; 196(1): 118-123.
MacArthur J, Bowler E, Cerezo M, Gil L, Hall P, Hastings E, Junkins H, McMahon A, Milano A, Morales J, et al. The new NHGRI-EBI Catalog of published genome-wide association studies (GWAS Catalog). Nucleic Acids Res. 2017; 45(D1): D896-D901.
Madore F, Stampfer MJ, Rimm EB, Curhan GC. Nephrolithiasis and risk of hypertension. Am J Hypertens. 1998; 11(1 Pt 1): 46-53.
Matsumoto S, Abe Y, Fujibuchi T, Takeuchi T, Kito K, Ueda N, Shigemoto K, Gyo K. Characterization of a MAPKK-like protein kinase TOPK. Biochem Biophys Res Commun. 2004; 325(3): 997-1004.
Mesiano S, Wang Y, Norwitz ER. Progesterone receptors in the human pregnancy uterus: do they hold the key to birth timing? Reprod Sci. 2011; 18(1): 6-19.
Mossetti G, Rendina D, Viceconti R, Manno G, Guadagno V, Strazzullo P, Nunziata V. The relationship of 3' vitamin D receptor haplotypes to urinary supersaturation of calcium oxalate salts and to age at onset and familial prevalence of nephrolithiasis. Nephrol Dial Transplant. 2004; 19(9): 2259-2265.
National statistical office. 2021. Web site: http://www.nso.go.th (June,2021)
Nettuwakul C, Praditsap O, Sawasdee N, Rungroj N, Ruamyod K, Watanapa WB, Junking M, Sangnual S, Sritippayawan S, Cheunsuchon B, et al. Loss-of-function mutations of SCN10A encoding NaV1.8 alpha subunit of voltage-gated sodium channel in patients with human kidney stone disease. Sci Rep. 2018; 8(1): 10453.
Nettuwakul C, Sawasdee N, Praditsap O, Rungroj N, Pasena A, Dechtawewat T, Deejai N, Sritippayawan S, Rojsatapong S, Chaowagul W, et al. A novel loss-of-function mutation of PBK associated with human kidney stone disease. Sci Rep. 2020; 10(1): 10282.
Nicolaidou P, Themeli S, Karpathios T, Georgouli H, Athanassaki K, Xaidara A, Messaritakis J. Family pattern of idiopathic hypercalciuria and its subtypes. J Urol . 1996; 155(3): 1042-1044.
Nimmannit S, Malasit P, Susaengrat W, Ong-Aj-Yooth S, Vasuvattakul S, Pidetcha P, Shayakul C, Nilwarangkur S. Prevalence of endemic distal renal tubular acidosis and renal stone in the northeast of Thailand. Nephron. 1996; 72(4): 604-610.
Pang Y, Dong J, Thomas P. Characterization, neurosteroid binding and brain distribution of human membrane progesterone receptors delta and {epsilon} (mPRdelta and mPR{epsilon}) and mPRdelta involvement in neurosteroid inhibition of apoptosis. Endocrinology. 2013; 154(1): 283-295.
Pungsrinont T, Nettuwakul C, Sawasdee N, Rungroj N, Sritippayawan S, Yenchitsomanus P T. Association between intelectin-1 variation and human kidney stone disease in northeastern Thai population. Urolithiasis. 2021.
Reed BY, Heller HJ, Gitomer WL, Pak CY. Mapping a gene defect in absorptive hypercalciuria to chromosome 1q23.3-q24. J Clin Endocrinol Metab. 1999; 84(11): 3907-3913.
Romero V, Akpinar H, Assimos DG. Kidney stones: a global picture of prevalence, incidence, and associated risk factors. Rev Urol. 2010; 12(2-3): e86-96.
Rule AD, Bergstralh EJ, Melton LJ, 3rd, Li X, Weaver AL, Lieske JC. Kidney stones and the risk for chronic kidney disease. Clin J Am Soc Nephrol. 2009; 4(4): 804-811.
Rule AD, Roger VL, Melton LJ, 3rd, Bergstralh EJ, Li X, Peyser PA, Krambeck AE, Lieske JC. Kidney stones associate with increased risk for myocardial infarction. J Am Soc Nephrol. 2010; 21(10): 1641-1644.
Rungroj N, Nettuwakul C, Sawasdee N, Sritippayawan S, Yenchitsomanus PT. Correlation between genotypes of F2 rs5896 (p.Thr165Met) polymorphism and urinary prothrombin fragment 1. Urolithiasis. 2018; 46(4): 405-407.
Rungroj N, Nettuwakul C, Sudtachat N, Praditsap O, Sawasdee N, Sritippayawan S, Chuawattana D, Yenchitsomanus PT. A whole genome SNP genotyping by DNA microarray and candidate gene association study for kidney stone disease. BMC Med Genet. 2014; 15: 50.
Rungroj N, Sritippayawan S, Thongnoppakhun W, Paemanee A, Sawasdee N, Nettuwakul C, Sudtachat N, Ungsupravate D, Praihirunkit P, Chuawattana D, et al. Prothrombin haplotype associated with kidney stone disease in Northeastern Thai patients. Urology. 2011; 77(1): 249 e217-223.
Rungroj N, Sudtachat N, Nettuwakul C, Sawasdee N, Praditsap O, Jungtrakoon P, Sritippayawan S, Chuawattana D, Borvornpadungkitti S, Predanon C, et al. Association between human prothrombin variant (T165M) and kidney stone disease. PLoS One. 2012; 7(9): e45533-e45533.
Saigal CS, Joyce G, Timilsina AR, Urologic Diseases in America P. Direct and indirect costs of nephrolithiasis in an employed population: opportunity for disease management? Kidney Int. 2005; 68(4): 1808-1814.
Sayer JA. Progress in Understanding the Genetics of Calcium-Containing Nephrolithiasis. J Am Soc Nephrol. 2017; 28(3): 748-759.
Scales CD, Jr., Smith AC, Hanley JM, Saigal CS, Urologic Diseases in America P. Prevalence of kidney stones in the United States. Eur Urol. 2012; 62(1): 160-165.
Shughrue PJ, Stumpf WE, Sar M. The distribution of progesterone receptor in the 20-day-old fetal mouse: an autoradiographic study with [125I]progestin. Endocrinology. 1988; 123(5): 2382-2389.
Sriboonlue P, Prasongwatana V, Chata K, Tungsanga K. Prevalence of upper urinary tract stone disease in a rural community of north-eastern Thailand. Br J Urol. 1992; 69(3): 240-244.
Sriboonlue P, Prasongwatana V, Suwantrai S, Bovornpadungkitti S, Tungsanga K, Tosukhowong P. Nutritional potassium status of healthy adult males residing in the rural northeast Thailand. J Med Assoc Thai. 1998; 81(3): 223-232.
Sriboonlue P, Prasongwattana V, Tungsanga K, Tosukhowong P, Phantumvanit P, Bejraputra O, Sitprija V. Blood and urinary aggregator and inhibitor composition in controls and renal-stone patients from northeastern Thailand. Nephron. 1991; 59(4): 591-596.
Sritippayawan S, Borvornpadungkitti S, Paemanee A, Predanon C, Susaengrat W, Chuawattana D, Sawasdee N, Nakjang S, Pongtepaditep S, Nettuwakul C, et al. Evidence suggesting a genetic contribution to kidney stone in northeastern Thai population. Urol Res. 2009; 37(3): 141-146.
Stapleton A, Ryall U. Blood coagulation proteins and urolithiasis are linked: crystal matrix protein is the Fl activation peptide of human prothrombin. Br J Urol. 1995; 75(6): 712-719.
Stewart CS, Duncan SH, Cave DR. Oxalobacter formigenes and its role in oxalate metabolism in the human gut. FEMS Microbiol Lett. 2004; 230(1): 1-7.
Suzuki K, Moriyama M, Nakajima C, Kawamura K, Miyazawa K, Tsugawa R, Kikuchi N, Nagata K. Isolation and partial characterization of crystal matrix protein as a potent inhibitor of calcium oxalate crystal aggregation: evidence of activation peptide of human prothrombin. Urol Res. 1994; 22(1): 45-50.
Taguchi K, Yasui T, Milliner DS, Hoppe B, Chi T. Genetic risk factors for idiopathic urolithiasis: A systematic review of the literature and causal network analysis. Eur Urol Focus. 2017; 3(1): 72-81.
Tang YT, Hu T, Arterburn M, Boyle B, Bright JM, Emtage PC, Funk W D. PAQR proteins: a novel membrane receptor family defined by an ancient 7-transmembrane pass motif. J Mol Evol. 2005; 61(3): 372-380.
Tencza AL, Ichikawa S, Dang A, Kenagy D, McCarthy E, Econs MJ, Levine MA. Hypophosphatemic rickets with hypercalciuria due to mutation in SLC34A3/type IIc sodium-phosphate cotransporter: presentation as hypercalciuria and nephrolithiasis. J Clin Endocrinol Metab. 2009; 94(11): 4433-4438.
Torricelli FC, Reichard C, Monga M. Urolithiasis in complicated inflammatory bowel disease: a comprehensive analysis of urine profile and stone composition. Int Urol Nephrol. 2021; 53(2): 205-209.
Tosukhowong P, Borvonpadungkitti S, Prasongwatana V, Tungsanga K, Jutuporn S, Dissayabutr T, Reungjui S, Sriboonlue P. Urinary citrate excretion in patients with renal stone: roles of leucocyte ATP citrate lyase activity and potassium salts therapy. Clin Chim Acta. 2002; 325(1-2): 71-78.
Trinchieri A, Ostini F, Nespoli R, Rovera F, Montanari E, Zanetti G. A prospective study of recurrence rate and risk factors for recurrence after a first renal stone. J Urol. 1999; 162(1): 27-30.
Tsuji S, Uehori J, Matsumoto M, Suzuki Y, Matsuhisa A, Toyoshima K, Seya T. Human intelectin is a novel soluble lectin that recognizes galactofuranose in carbohydrate chains of bacterial cell wall. J Biol Chem. 2001; 276(26): 23456-23463.
Udomsilp P, Saepoo S, Ittiwut R, Shotelersuk V, Dissayabutra T, Boonla C, Tosukhowong P. rs11567842 SNP in SLC13A2 gene associates with hypocitraturia in Thai patients with nephrolithiasis. Genes Genomics. 2018; 40(9): 965-972.
Vezzoli G, Terranegra A, Rainone F, Arcidiacono T, Cozzolino M, Aloia A, Dogliotti E, Cusi D, Soldati L. Calcium-sensing receptor and calcium kidney stones. J Transl Med. 2011; 9: 201.
Wang S, Wang X, Wu J, Lin Y, Chen H, Zheng X, Zhou C, Xie L. Association of vitamin D receptor gene polymorphism and calcium urolithiasis in the Chinese Han population. Urol Res. 2012; 40(4): 277-284.
Wesener DA, Wangkanont K, McBride R, Song X, Kraft MB, Hodges HL, Zarling LC, Splain RA, Smith DF, Cummings RD, et al. Recognition of microbial glycans by human intelectin-1. Nat Struct Mol Biol. 2015; 22(8): 603-610.
Wolf MT, Zalewski I, Martin FC, Ruf R, Muller D, Hennies HC, Schwarz S, Panther F, Attanasio M, Acosta HG, et al. Mapping a new suggestive gene locus for autosomal dominant nephrolithiasis to chromosome 9q33.2-q34.2 by total genome search for linkage. Nephrol Dial Transplant. 2005; 20(5): 909-914.
Xu C, Song R-j, Yang J, Jiang B, Wang X-l, Wu W, Zhang W. Klotho gene polymorphism of rs3752472 is associated with the risk of urinary calculi in the population of Han nationality in Eastern China. Gene. 2013; 526(2): 494-497.
Yanagawa M, Kawamura J, Onishi T, Soga N, Kameda K, Sriboonlue P, Prasongwattana V, Borwornpadungkitti S. Incidence of urolithiasis in northeast Thailand. Int J Urol. 1997; 4(6): 537-540.
Yasui T, Okada A, Urabe Y, Usami M, Mizuno K, Kubota Y, Tozawa K, Sasaki S, Higashi Y, Sato Y. A replication study for three nephrolithiasis loci at 5q35. 3, 7p14. 3 and 13q14. 1 in the Japanese population. J Hum Genet. 2013; 58(9): 588-593.
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