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GRHPR gene variations in Iraqi patients infected with calcium oxalate kidney stones


  • Duha Abed Almuhssen Muzahim Alzubaidy Department of Biology, College of Science for Women, University of Baghdad, Baghdad, Iraq.
  • Luma Hassan Alwan Al Obaidy Department of Biology, College of Science for Women, University of Baghdad, Baghdad, Iraq.



ELISA, GRHPR enzyme concentration, GRHPR gene variation, kidney stone, PCR


      The alterations in glyoxylate reductase and hydroxy-pyruvate reductase concentrations in the sera and the genetic alterations associated with calcium oxalate kidney stones in Iraqi patients were not studied previously so this study aimed to focus on these points. This study included 80 subjects; they were 50 patients with calcium oxalate stones compared to 30 apparently healthy controls. Biochemical investigations for kidney functions (creatinine, urea, and uric acid), were performed on the sera of both groups. Also, complete blood count, random blood sugar, and blood group tests. Furthermore, urine had been collected for General Urine Examination to visualize oxalate crystals in the urine of the patient. Also, the GRHPR enzyme concentration was measured by ELISA for both groups. The DNA was isolated from whole blood and the target DNA was amplified by PCR then the pathogenic mutations at c.295C>T (rs119490108), c.165G>A (rs180177314) and c.904C>T (p. Arg302Cys) rs180177322 were investigated by direct sequencing of the product, and then the results were analyzed. This study found that the concentration of the enzyme in the controls (4.78 ± 1.06 mg/dl) was significantly higher than its concentration in the patients (0.411 ± 0.02mg/dl). The pathogenic mutations were not found in both studied groups, but other positions were found polymorphic; at exon 4 the rs2768659 (A>G), rs1294628807 (G>A) and rs2736664 (C>T), at exon 6: c.579A>G (p. Ala193=) rs309458 and c.494-68A>G rs309459 and at exon 9 c.*146A>G rs1057507. In conclusion, this study found that calcium oxalate stones were associated with decrease GRHPR enzyme concentration in the patients compared to the control group which may be caused by mutations or epigenetics masking of the gene expression.


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Stamatelou K, Goldfarb DS. Epidemiology of Kidney Stones. Healthc. 2023; 11(3): 424.

Wang K, Ge J, Han W, Wang D, Zhao Y, Shen Y, et al. Risk factors for kidney stone disease recurrence: a comprehensive meta-analysis. BMC Urol. 2022; 22(62):1-13.

Singh P, Harris PC, Sas DJ, Lieske JC. The genetics of kidney stone disease and nephrocalcinosis. Nat Rev Nephrol. 2022; 18(4): 224-40.

Moftakhar L, Jafari F, Johari MG, Rezaeianzadeh R, Hosseini SV, Rezaianzadeh A. Prevalence and risk factors of kidney stone disease in population aged 40–70 years old in Kharameh cohort study: a cross-sectional population-based study in southern Iran. BMC Urol. 2022; 22(1): 1-9.

Moghadam TZ, Pourfarzi F, Rad HM, Zandian H. Kidney stones among Iranian adults: Prevalence and socioeconomic inequality assessment in a cohort‐based cross‐sectional study. Health Sci Rep. 2022; 5(6): e877:1-9.

Cabo J, His R, Nashville TN. The Financial Burden of Patients with Kidney Stones and Association with Health-Related Quality of Life. J Urol. 2022; 207(5s): e446.

Geraghty RM, Cook P, Roderick P, Somani B. Risk of metabolic syndrome in kidney stone formers: a comparative cohort study with a median follow-up of 19 years. J Clin Med Res. 2021; 10(5) :978.

Lin BB, Lin ME, Huang RH, Hong YK, Lin BL, He XJ. Dietary and lifestyle factors for primary prevention of nephrolithiasis: a systematic review and meta-analysis. BMC nephrology. 2020; 21(267): 1-13.

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; 292953: 1-21.

Carvalho M, Vieira MA. Changes in Calcium Oxalate Crystal Morphology as a Function of Supersaturation. Braz J Urol. 2004; 30 (3): 205-209.

Lai Y, Zheng H, Sun X, Lin J, Li Q, Huang H, et al. The advances of calcium oxalate calculi associated drugs and targets, Eur J Pharmacol. 2022; 935: 175324.

Gay C, Letavernier E, Verpont MC, Walls M, Bazin D, Daudon M, et al. Nanoscale analysis of Randall’s plaques by electron energy loss Spectro microscopy: insight in early biomineral formation in human kidney. ACS nano. 2020; 14(2): 1823-36.

Afaj AH, Sultan MA. Mineralogical Composition of the Urinary Stones from Different Provinces in Iraq. Sci World J. 2005; 5: 24–38.

Laohapan A, Nuwatkrisin K, Ratchanon S, Usawachintachit M. Study of urinary stone composition in a university based hospital. Insight Urol. 2020; 41(2): 48-56.

Zhang D, Li S, Zhang Z, Li N, Yuan X, Jia Z, et al. Urinary stone composition analysis and clinical characterization of 1520 patients in central China. Sci Rep. 2021; 11(1): 6467.

Palmer BF, Kelepouris E, Clegg DJ Renal Tubular Acidosis and Management Strategies: A Narrative Review. Adv Ther. 2021; 38(2): 949–968.

Alelign T, Petros B. Kidney Stone Disease: An Update on Current Concepts. Adv Urol. 2018; ID3068365: 1-12.

Takayama T, Takaoka N, Nagata M, Johnin K, Okada Y, Tanaka S, et al. Ethnic differences in GRHPR mutations in patients with primary hyperoxaluria type 2. Clin Genet. 2014 ; 86(4): 342-8.

Juliebø‑Jones P,Somani BK, Baug S,Beisland C, Ulvik Ø. Management of Kidney Stone Disease in Pregnancy: A Practical and Evidence‑Based Approach. Curr Urol Rep. 2022; 23(11): 263–270.

Kovesdy CP. Epidemiology of chronic kidney disease: an update. Kidney Int. 2022; 12(1): 7–11.

Khalili P, Jamali Z, Sadeghi T, Esmaeili-Nadimi A, Mohamadi M, Moghadam-Ahmadi A, et al. Risk factors of kidney stone disease: a cross-sectional study in the southeast of Iran. BMC Urol. 2021; 21: 1-8.

Kaufman J, Vicedo‑Cabrera AM, Tam V, Song L, Cofel E, Tasian G. The impact of heat on kidney stone presentations in South Carolina under two climate change scenarios. Sci Rep. 2022; 12(1): 369.

Han H, Sega AM, Seifter JL, Dwyer JT. Nutritional Management of Kidney Stones (Nephrolithiasis). Clin Nutr Res 2015; 4(3): 137-152.

Ferraro PM, Bargagli M, Trinchieri A, Gambaro G. Risk of kidney stones: influence of dietary factors, dietary patterns, and vegetarian–vegan diets. Nutrients. 2020; 12(3): 779.

Shahidi S, Dolatkhah S, Mortazavi M, Atapour A, Aghaaliakbari F, Meamar R, et al. An epidemiological survey on kidney stones and related risk factors in the Iranian community. Acta Med Iran. 2022; 60(5): 307-12.

Diangienda PK, Moningo DM, Mayindu AN, Makulo JR, Sumaili EK, Mafuta EM, Loposso MN, Punga-Maole AM, Lufuma SL, Haymann JP, Daudon M. Eating Habits among Lithiasic Patients in Kinshasa, the Democratic Republic of Congo. Open J Urol. 2021; 11(6): 200-13.

Ebrahimi M, Yasseri AF, Baghdadabad LZ, Zahmatkesh P, Pakseresht BK, Khoshchehreh M, et al, The Impact of Potassium Citrate on the Kidney Stones Treatment in Rat. Transl Androl Urol. 2021; 3(4): 176-81.

Baatiah NY, Alhazmi RB, Albathi FA, Albogami EG, Mohammedkhalil AK, Alsaywid BS. Urolithiasis: Prevalence, risk factors, and public awareness regarding dietary and lifestyle habits in Jeddah, Saudi Arabia in 2017. Urol Ann. 2020 ; 12(1): 57.

Gamage KN, Jamnadass E, Sulaiman SK, Pietropaolo A, Aboumarzouk O, Somani BK, The role of fluid intake in the prevention of kidney stone disease: A systematic review over the last two decades. Turk J Urol. 2020; 46(Suppl 1): S92–S103.

Siener R. Nutrition and Kidney Stone Disease. Nutrients. 2021; 13(6): 1917.

Espinosa-Ortiz EJ, Eisner BH, Lange D, Gerlach R. Current insights into the mechanisms and management of infection stones. Nat Rev Urol 2019; 16(1): 35-53.

Daudon M, Petay M, Vimont S, Deniset A, Tielens F, Haymann JP, et al. Urinary tract infection inducing stones: Some clinical and chemical data. C R Chim. 2022; 25(S1): 315-34.

Dobrek Ł. Kidney stone disease with special regard to drug-induced kidney stones—A contemporary synopsis. Wiad Lek. 2020; 73(9 p II): 2031-9.

Schott C, Pourtousi A, Connaughton DM. Monogenic causation of pediatric nephrolithiasis.2022; Front Urol. 2: 1075711: 1-22.

Konkoľová J, Chandoga J, Kováčik J, Repiský M, Kramarová V, Paučinová I, et al, Severe child form of primary hyperoxaluria type 2 - a case report revealing consequence of GRHPR deficiency on metabolism. BMC Med Genet. 2017; 18(59): 1-11.

Köttgen A. Genetics in chronic kidney disease: conclusions from a Kidney Disease: Improving Global Outcomes (KDIGO) Controversies Conference. Kidney Int. 2022; 101: 1126–1141.

Chatterjee A, Sarkar K, Bank S, Ghosh S, Kumar Pal D, Saraf S, et al. Homozygous GRHPR C. 494G> A mutation is deleterious that causes early onset of nephrolithiasis in West Bengal, India. Front Mol Neurosci. 2022; 9: 1049620.

Cramer SD, Ferree PM, Lin K, Milliner DS, Holmes RP. The Gene Encoding Hydroxypyruvate Reductase (GRHPR) is Mutated in Patients with Primary Hyperoxaluria Type II. Hum Mol Gen. 1999; 8 (11): 2063–2069.

Shee k, Stoller ML. Perspectives in primary hyperoxaluria — historical, current and future clinical interventions. Nat Rev Urol .2022; 19: 137–146.

Abid A, Raza A, Khan AR, Firasa S, Shahid S, Hashmi S, et al. Primary hyperoxaluria: Comprehensive mutation screening of the disease-causing genes and spectrum of disease-associated pathogenic variants. Clin Gen. 2022; 103(1): 53-66.

Takayama T, Nagata M, Ozono S, Nonomura K, Cramer SD. A novel mutation in the GRHPR gene in a Japanese patient with primary hyperoxaluria type 2. Nephrol Dial Transplant. 2007; 22(8): 2371-4.

Garrelfs SF, Rumsby G, Peters-Sengers H, Erger F, Groothoff JW, Beck BB, et al. Patients with primary hyperoxaluria type 2 have significant morbidity and require careful follow-up. Kidney Int. 2019; 6 (6): 1389-99.

Wang J, Wang Y, Xing P, Liu Q, Zhang C, Sui Y, et al. Development and validation of a hypoxia related prognostic signature for breast cancer. Oncol Lett. 2020; 20(2): 1906-14.

Pan Y, Ni R, Deng Q, Huang X, Zhang Y, Lu C, et al. Glyoxylate Reductase/Hydroxypyruvate Reductase: A Novel Prognostic Marker for Hepatocellular Carcinoma Patients after Curative Resection. Pathobiol .2013; 80 (3): 155–162.

Yang S, Liu Y, Zhang B, Li J, Xu F, Yu M, Chen Y, et al. GRHPR, targeted by miR-138-5p, inhibits the proliferation and metastasis of hepatocellular carcinoma through PI3K/AKT signaling pathway.

Res Sq. 2022: 1-21. Preprint copy.

Gianmoena K, Gasparoni N, Jashari A, Gabrys P, Grgas K, Ghallab A, et al. Epigenomic and transcriptional profiling identifies impaired glyoxylate detoxification in NAFLD as a risk factor for hyperoxaluria. Cell Rep. 2021; 36(109526): 1-28.

Lee AJ, Yoo EH, Bae YC, Jung SB, Jeon,CH.. Differential identification of urine crystals with morphologic characteristics and solubility test. J Clin Lab Anal. 2022; 36: e24707.

Dawson CH, Tomson CR. Kidney stone disease: pathophysiology, investigation and medical treatment. Clin Med. 2012; 12(5): 467.

Wesson JA, Kolbach-Mandel AM, Hoffmann BR, Davis C, Mandel NS. Selective protein enrichment in calcium oxalate stone matrix: a window to pathogenesis? Urolithiasis. 2019; 47(6): 521–532.

Önal B, Kırlı EA. Pediatric stone disease: Current management and future concepts. Turk Arch Pediatr. 2021; 56(2): 99-107.

Alani, M.S. and Al-Mayaly, I.K., 2022. Detection of Albumin and Urea in Kidney Failure Patients by Optical Biosensor. Iraqi J Sci. 63(1), pp.43-52.

Waikar SS, Srivastava A, Palsson, R, Shafi T, Hsu C, Sharma K, et al. Association of Urinary Oxalate Excretion with the Risk of Chronic Kidney Disease Progression for the Chronic Renal Insufficiency Cohort study investigators. JAMA Intern Med. 2019; 179(4): 542-551.

Al-Taiee TA, Al-Shammaa NM. Effect of Anti Diuretic Hormone (ADH) in Kidney Function on Post Hemodialysis End Stage Renal Failure Disease (ESRD) Iraqi Patients. Iraqi J Med Sci. 2018(3B): 1372-7.

Park C, Ha Y, Kim Y, Yun S, Lee S, Kim W. Comparison of Metabolic Risk Factors in Urolithiasis Patients according to Family History, Korean J Urol: 2010; 51(1): 50-53.

Salih, S.S. and Yenzeel, J.H., 2020. Evaluation of Thyroid Hormones and Some Biochemical Variables in Patients with Chronic Kidney Disease. Iraqi Journal of Science, pp.985-992.

Halbritter J, Seidel A, Müller L, Schönauer R, Hoppe B. Update on Hereditary Kidney Stone Disease and Introduction of a New Clinical Patient Registry in Germany, Front. Pediatr. 2018; 6(47): 1-7.

Bommer GT, Schaftingen V, Veiga-da-Cunha M. Metabolite Repair Enzymes Control Metabolic Damage in Glycolysis. Trends Biochem Sci. 2020. 45 (3): 224-243.

Cregeen DP, Williams EL, HultonS, Rumsby G. Molecular Analysis of the Glyoxylate Reductase (GRHPR) Gene and Description of Mutations Underlying Primary. Hum Mutat. 2003; 22(6) :1-9.

Mandrile G, Beck B, Acquaviva C, Rumsby G, Deesker L, Garrelfs S, et al. Genetic assessment in primary hyperoxaluria: why it matters. Pediatr Nephrol. 2023; 38: 625–634.