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J Am Soc Nephrol 10:2120-2124, 1999
© 1999 American Society of Nephrology

Polymorphisms in the Genes Encoding for Human Kinin Receptors and the Risk of End-Stage Renal Failure

Results of Transmission/DisequilibriumTest

MARCIN J. ZYCHMA, JANUSZ GUMPRECHT, EWA ZUKOWSKA-SZCZECHOWSKA, WLADYSLAW GRZESZCZAK and THE END-STAGE RENAL DISEASE STUDY GROUPa

Department and Clinic of Internal Medicine and Diabetology, Silesian School of Medicine, Zabrze, Poland.

Correspondence to Dr. Wladyslaw Grzeszczak, Department and Clinic of Internal Medicine and Diabetology, 3-go Maja 13-15, 41-800 Zabrze, Poland. Phone: +48 32 271 2511; Fax: +48 32 271 4611; E-mail: reklin{at}infomed.slam.katowice.pl

Abstract. There is evidence that environmental factors and genetic predisposition affect the development of end-stage renal disease (ESRD). The role of kinin peptides in renal pathology has been also suggested, and a nephroprotective effect of kinins, mediated by B1 and B2 kinin receptors, has been postulated. Recently, two novel sequence differences in the B1R gene were identified, and the C allele of the G->C substitution at position -699 in the promoter region of the B1R gene was found to be less frequent among patients with ESRD compared with healthy control subjects. In this study, the association between B1R and B2R polymorphisms and ESRD was examined using a family-based study design: transmission/disequilibrium test. B1R gene G->C substitution at position -699 in the promoter region and B2R gene C->T transition at position 181 in exon 2 were genotyped in 247 family trios: offspring affected with ESRD and both parents. The less common alleles of both polymorphisms (B1R C allele and B2R T allele) were transmitted from heterozygous parents to offspring affected with ESRD less frequently than expected (37 and 36%, respectively; P < 0.05). In conclusion, results obtained in this study support a hypothesis of the protective role of bradykinin receptor gene polymorphisms in the development of ESRD.




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