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A Genome-Wide Association Study of Nephrolithiasis in the Japanese Population Identifies Novel Susceptible Loci at 5q35.3, 7p14.3, and 13q14.1


Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51×10−12, odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16×10−14, OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62×10−9, OR = 1.14). Subsequent analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443 with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54×10−8), suggesting a crucial role for this variation in renal function. Our findings elucidated the significance of genetic variations for the pathogenesis of nephrolithiasis.


Vyšlo v časopise: A Genome-Wide Association Study of Nephrolithiasis in the Japanese Population Identifies Novel Susceptible Loci at 5q35.3, 7p14.3, and 13q14.1. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002541
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002541

Souhrn

Nephrolithiasis is a common nephrologic disorder with complex etiology. To identify the genetic factor(s) for nephrolithiasis, we conducted a three-stage genome-wide association study (GWAS) using a total of 5,892 nephrolithiasis cases and 17,809 controls of Japanese origin. Here we found three novel loci for nephrolithiasis: RGS14-SLC34A1-PFN3-F12 on 5q35.3 (rs11746443; P = 8.51×10−12, odds ratio (OR) = 1.19), INMT-FAM188B-AQP1 on 7p14.3 (rs1000597; P = 2.16×10−14, OR = 1.22), and DGKH on 13q14.1 (rs4142110; P = 4.62×10−9, OR = 1.14). Subsequent analyses in 21,842 Japanese subjects revealed the association of SNP rs11746443 with the reduction of estimated glomerular filtration rate (eGFR) (P = 6.54×10−8), suggesting a crucial role for this variation in renal function. Our findings elucidated the significance of genetic variations for the pathogenesis of nephrolithiasis.


Zdroje

1. YoshidaOTeraiAOhkawaTOkadaY 1999 National trend of the incidence of urolithiasis in Japan from 1965 to 1995. Kidney Int 56 1899 1904

2. StrohmaierWL 2000 Course of calcium stone disease without treatment. What can we expect? Eur Urol 37 339 344

3. CoeFLEvanAWorcesterE 2005 Kidney stone disease. J Clin Invest 115 2598 2608

4. ZilbermanDEYongDAlbalaDM The impact of societal changes on patterns of urolithiasis. Curr Opin Urol 20 148 153

5. TaylorENStampferMJCurhanGC 2005 Obesity, weight gain, and the risk of kidney stones. JAMA 293 455 462

6. CurhanGCWillettWCRimmEBStampferMJ 1997 Family history and risk of kidney stones. J Am Soc Nephrol 8 1568 1573

7. GoldfarbDSFischerMEKeichYGoldbergJ 2005 A twin study of genetic and dietary influences on nephrolithiasis: a report from the Vietnam Era Twin (VET) Registry. Kidney Int 67 1053 1061

8. ThorleifssonGHolmHEdvardssonVWaltersGBStyrkarsdottirU 2009 Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density. Nat Genet 41 926 930

9. Yamaguchi-KabataYNakazonoKTakahashiASaitoSHosonoN 2008 Japanese population structure, based on SNP genotypes from 7003 individuals compared to other ethnic groups: effects on population-based association studies. Am J Hum Genet 83 445 456

10. TeraiAOkadaYOhkawaTOgawaOYoshidaO 2000 Changes in the incidence of lower urinary tract stones in japan from 1965 to 1995. Int J Urol 7 452 456

11. ChouYHSuCMLiCCLiuCCLiuME 2011 Difference in urinary stone components between obese and non-obese patients. Urol Res 39 283 287

12. KamataniYMatsudaKOkadaYKuboMHosonoN 2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nature Genetics 42 210 U225

13. PriéDHuartVBakouhNPlanellesGDellisO 2002 Nephrolithiasis and osteoporosis associated with hypophosphatemia caused by mutations in the type 2a sodium-phosphate cotransporter. N Engl J Med 347 983 991

14. BeckLKaraplisACAmizukaNHewsonASOzawaH 1998 Targeted inactivation of Npt2 in mice leads to severe renal phosphate wasting, hypercalciuria, and skeletal abnormalities. Proc Natl Acad Sci U S A 95 5372 5377

15. KöttgenAPattaroCBögerCAFuchsbergerCOldenM 2010 New loci associated with kidney function and chronic kidney disease. Nat Genet 42 376 384

16. KestenbaumBGlazerNLKöttgenAFelixJFHwangSJ 2010 Common genetic variants associate with serum phosphorus concentration. J Am Soc Nephrol 21 1223 1232

17. MaTYangBGillespieACarlsonEJEpsteinCJ 1998 Severely impaired urinary concentrating ability in transgenic mice lacking aquaporin-1 water channels. J Biol Chem 273 4296 4299

18. BerridgeMJ 1989 The Albert Lasker Medical Awards. Inositol trisphosphate, calcium, lithium, and cell signaling. JAMA 262 1834 1841

19. BarnettJHSmollerJW 2009 The genetics of bipolar disorder. Neuroscience 164 331 343

20. De JagerPLChibnikLBCuiJReischlJLehrS 2009 Integration of genetic risk factors into a clinical algorithm for multiple sclerosis susceptibility: a weighted genetic risk score. Lancet Neurol 8 1111 1119

21. FinkHAAkornorJWGarimellaPSMacDonaldRCuttingA 2009 Diet, fluid, or supplements for secondary prevention of nephrolithiasis: a systematic review and meta-analysis of randomized trials. Eur Urol 56 72 80

22. NakamuraY 2007 The BioBank Japan Project. Clin Adv Hematol Oncol 5 696 697

23. SakhaeeK 2008 Nephrolithiasis as a systemic disorder. Curr Opin Nephrol Hypertens 17 304 309

24. OkadaYHirotaTKamataniYTakahashiAOhmiyaH 2011 Identification of nine novel loci associated with white blood cell subtypes in a Japanese population. PLoS Genet 7 e1002067 doi:10.1371/journal.pgen.1002067

25. PurcellSNealeBTodd-BrownKThomasLFerreiraM 2007 PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81 559 575

26. McCarthyMIAbecasisGRCardonLRGoldsteinDBLittleJ 2008 Genome-wide association studies for complex traits: consensus, uncertainty and challenges. Nature reviews Genetics 9 356 369

27. Pe'erIYelenskyRAltshulerDDalyMJ 2008 Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genetic epidemiology 32 381 385

28. BreslowNEDayNE 1987 Statistical methods in cancer research. Volume II–The design and analysis of cohort studies. IARC Sci Publ 1 406

29. ScottLJMohlkeKLBonnycastleLLWillerCJLiY 2007 A genome-wide association study of type 2 diabetes in Finns detects multiple susceptibility variants. Science 316 1341 1345

30. KamataniYMatsudaKOkadaYKuboMHosonoN 2010 Genome-wide association study of hematological and biochemical traits in a Japanese population. Nat Genet 42 210 215

31. MatsuoSImaiEHorioMYasudaYTomitaK 2009 Revised equations for estimated GFR from serum creatinine in Japan. Am J Kidney Dis 53 982 992

32. BarrettJFryBMallerJDalyM 2005 Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21 263 265

33. XuZTaylorJA 2009 SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37 W600 605

34. KelAEGösslingEReuterICheremushkinEKel-MargoulisOV 2003 MATCH: A tool for searching transcription factor binding sites in DNA sequences. Nucleic Acids Res 31 3576 3579

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Genetika Reprodukčná medicína

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PLOS Genetics


2012 Číslo 3
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