The Research On The Relationship Between Endothelin-A Receptor Gene Polymorphisms In Children With Primary Nephrotic Syndrome

Object: The aim of this study was to investigate the relationship betweenendothelin-A receptor gene polymorphisms in locus rs1801708, rs5335, rs5343,rs10305936and the morbidity and progress of primary nephrotic syndrome.providung valid scientific basis for futher investigation of the pathogenesis of PNS.Method:62children with primary nephrotic syndrome were enrolled as case group,including39males and23females, the mean age is（5.32±3.74）. the patients weredivided into simple type NS group(35case) and nephritic type NS group(27case)；non-resistance NS group(40case) and steroid resistance NS group (22case)；thenon-hypertension group(44case) and hypertension group (18case).50healthychildren were selected as control group. All subject were genotyped for endothelin-Areceptor gene polymorphisms in locus rs1801708, rs5335, rs5343, rs10305936byusing the polymerase chain reaction (PCR) and drict gene sequence test technique.Monitoring a number of clinical indicators at active stage, such as blood pressure, thequantity of protein in a24-hour urine, plasma albumin, blood urea nitrogen, serumcreatinine, total cholesterol in plasma, triglyceride, high-density lipoproteincholesterol and low-density lipoprotein cholesterol the same time.Result：1. In locus rs1801708of endothelin-A receptor gene, the frequencies of GG, AG, AAgenotype on cases group and control group were38.7%,48.4%,12.9%,and50.0%,42.0%,8.0%respectively. There was no statistically significant difference in genotypedistribution and allele frequence distribution within cases group and controlgroup,male NS group and female NS group,simple type NS group and nephritis typeNS group, the non-steroid resistant NS group and steroid resistant NS group,thenon-hypertension group and hypertension group (P>0.05).2. In locus rs rs5335of endothelin-A receptor gene, the frequencies of CC, CG, GGgenotype on cases group and control group were25.8%,56.5%,17.7%and8.0%.76.0%,16.0%,respectively,the difference between these two groups werestatistical significance(2=6.59,P=0.037<0.05). Compared to the CG genotype,theCC genotype increased the risk to PNS with OR of4.34times(95%CI was1.32-14.25), also Compared to the GG genotype,the CC genotype increased the risk to PNS with OR of2.91(95%CI was time0.70-12.90). There was no statisticallysignificant difference in genotype distribution and allele frequence distribution withinmale NS group and female NS group,simple type NS group and nephritis type NSgroup, the non-steroid resistant NS group and steroid resistant NS group,thenon-hypertension group and hypertension group (P>0.05).3. In locus rs rs5343of endothelin-A receptor gene, the frequencies of CC, CT, TTgenotype on cases group and control group were71.0%,27.4%,1.6%and95.0%,5.0%,0.0%,respectively. The genotype distribution frequence between thesetwo groups were statistical significant (2=6.34,P=0.042<0.05).The frequencies of C,T allele on cases group and control group were84.7%,15.3%and95.0%,5.0%,respectively, The C,T allele frequence between these two groups werestatistical significant（2=5.13,P=0.01<0.05）. Compared to the CC genotype,the CTgenotype increased the risk to PNS with OR of3.26times (95%CI was1.11-9.56), Tallele increaseed the risk to PNS at3.44times(95%CI was1.24-9.67). There was nostatistically significant difference in genotype distribution and allele frequencedistribution within male NS group and female NS group,simple type NS group andnephritis type NS group, the non-steroid resistant NS group and steroid resistant NSgroup,the non-hypertension group and hypertension group (P>0.05).4.In locus rs10305936,the genotype on cases Group and control group were both notconform to the Hardy-Weinbery law.5. Combined of GG genotype in locus rs1801708and CG genotype in locus5335,thedifference between cases group and control group on genotype distribution wasstatistical significance(2=5.79,P=0.016<0.05). Combined of GG genotype in locusrs1801708,CG genotype in locus5335, CC in locus5343,the difference between casesgroup and control group on genotype distribution was statistical significance (2=7.03,P=0.008<0.05).6. The difference between gene frequencies distribution in locus rs5335andhigh-density lipoprotein cholesterol level had statistical significance.The high-densitylipoprotein cholesterol on CC genotype were higher than the other genotype in casegroup.7. There were no significant differences between the age of morbidty, blood pressureand the quantity of24-hour urine protein, plasma albumin, blood urea nitrogen, serumcreatinine, total cholesterol in plasma, triglyceride and low-density lipoprotein cholesterol at active stage of PNS children among the each genotype of rs1801708、rs5335and rs5343three locus (P>0.05).Conclusion：1There was a significant relationship between the morbidity of PNS and the EDNRAgene polymorphism in locus rs5335, CC genotype may be a susceptible genetic factorfor patients with PNS.2There was a significant relationship between the morbidity of PNS and the EDNRAgene polymorphism in locus rs5343,CT genotype and T allele may be possible geneticsusceptibility factors for patients PNS.3There was no significant relationship between EDNRA gene polymorphism in locusrs1801708and PNS.4It can be proved that EDNRA gene polymorphism in locus rs5335is related to theplasma high density lipoprotein cholesterol (hdl-c).5There was no significant relationship between the age of morbidty, blood pressureand the quantity of24-hour urine protein, plasma albumin, blood urea nitrogen, serumcreatinine, total cholesterol in plasma, triglyceride and low-density lipoproteincholesterol at active stage of PNS children and the EDNRA gene polymorphism inlocus rs1801708, rs5335, rs5343.