The Relationship Between α-adducin Gene Polymorphism And Essential Hypertension

Objective:There are many factors that can cause essential hypertension, and the inherent factor and the environment factor are the two main factors which they interact each other and lead to essential hypertension. Adducin is a tetramer comprised of eitherα/βorα/γheterodimers. The metagons of the adducin had been discovered in red blood cells, brain, lungs, kidney and liver and so on. Adducin all contain an N-terminal globular head domain, a neck domain and a C-terminal protease-sensitive tail domain. Adducin activities can be regulated by PKC and PKA. Adducin is thought to regulate cell-to-cell contact, cell membrane ion transport, and signal transduction. A specific mutation (G614T) in the humanα-adducin gene has recently been described that results in the substitution of tryptohan(Try) for glycine(Gly) at amino acid number 460. A northern Chinese population were involved in this study. PCR-RFLP was used to detect the variant in the exon 10 ofα-adducin gene to investigate the the relationship betweenα-adducin in gene polymorphism and essential hypertension.Methods:160 patients with essential hypertension and 151 normotensive subjects were involved in this study. The criterion is 2005 Chinese Hypertension Guidelines and subjects have been diagnosed as hypertensive person and have used medicines for hypertension; subjects never use antihypertension drugs, the systolic pressure≥140 mmHg and/or diastolic pressure≥90 mmHg. The patients were those who fulfilled all of the following criteria: secondary hypertension, diabetes mellitus, cardiac disease, severe dysfunction of hepatic or renal. The involved subjects are the persons who do not meet the standard of primary hypertension and without family history of hypertension. Each selected subject has no kinship.We registered the clinical data and detected biochemical indicator of each subject, including: sex, age, family history, systolic blood pressure, diastolic blood pressure, triglyceride, total cholesterol, high dense lipoprotein cholesterol, low density lipoprotein cholesterol. All the patients must fast over 12 hours before the blood samples were obtained at 7:00-8:00 in the morning, and had laid on bed for 15 minutes at least, the blood samples were taken from median antebrachial vein. Each blood sample was predisposed according to the request of biochemical indicator detecting:centrifugalization, segregation supernatant, and the samples were kept in -80℃refrigerator, then waiting for the collecting to measure at the same time. Another 2ml anticoagulated blood was obtained for genome DNA extraction.Genomic DNA was isolated from 3ml of whole blood through orthodox phenol/chloroform methods. PCR-RFLP was used to detect the variant in the exon 10 ofα-adducin gene. The reagents in use are phosphonic acid buffer solution(PBS), proteinase K, extracting buffer, phenol, chloroform, isovaleric alcohol; Other reagents and instruments in use were the primers, dNTPs,DNA marker,RedTaq DNA polymerase, agarose, restriction enzyme, gene magnification meter, gel imaging system and so on.SAS 6.12 software pack was used to analyze all the data. All the continuous variables were expressed as mean±SEM. Gene counting method was used for gene frequency, and Chi-square test was used for analyzing allele frequency and analysis of categorical data. Students-t test was used for group comparison. A P-value of less than 0.05 was considered to be statistically significant.Results:1.There are no significant differences in the common clinical data and biochemical indicators between the two groups(P>0.05), including sex, age, family history, systolic blood pressure, diastolic blood pressure, triglyceride, total cholesterol, high dense lipoprotein cholesterol, low density lipoprotein cholesterol.2.Hardy-Weinberg equilibrium for the genotype distribution was assessed as before, the crowd which was selected was representative(P>0.05).3.There was no association in the three genotypes and allele frequencies between hypertensive and normotensive subjects(P>0.05).4.Compared with GlyGly genotypes, the SBP was higher in patients with GlyTrp and TrpTrp genotypes(P<0.01); Compared with GlyGly and TrpTrp genotypes, patients with GlyTrp genotypes had higher DBP(P<0.05).Conclusion : There was no association between theα-adducin Gly460Trp polymorphism and essential hypertension in a northern Chinese population; Hypertensive patients with 460Trp allele have higher SBP; Hypertensive patients with GlyTrp genotype have higher DBP.