Identification And Characteristics Of Single Nucleotide Polymorphisms Of Arachidonic Acid ω-Hydroxylase Genes Coding Region In Chinese Han Population

Objective Arachidonic acid Cytochrome P450 (CYP)ω-hydroxylases catalyze arachidonic acid to produce 19- and 20-HETE, especially the later. 19- and 20-HETE depolarize VSM by blocking the open-state probability of Ca²⁺-activated K⁺-channels. The formation of 19- and 20-HETE in vascular smooth muscle is enhanced by angiotensin II, endothelin and norepinephrine and is attenuated by nitric oxide (NO). 20-HETE plays an important role in the regulation of sodium reabsorption in renal tubules. 20-HETE inhibits Na⁺-K⁺-ATPase activity and sodium transport in proximal tubule. Additionally, 20-HETE may involve in a variety of pathophysiological conditions, especially primary hypertension. CYP4A11 and CYP4F2 became new interesting genes for hypertension, though we know little about them. Identification of characteristics single nucleotide polymorphisms (SNPs) existing in coding region of these genes may provide some new insights into the genetic mechanisms of hypertension.Method Genomic DNA was extracted from blood white cells of 50 unrelated Chinese Han people with normotension. The coding regions were amplified by PCR, respectively. After sequenced, the information wan aligned and summarized.Results Sixteen SNP sites in CYP4A11 were identified,in which there are 5 sense mutation, including A-54G in 5'-uncoding region, A6890C, A7207G, T7394A and T8590C , which caused corresponding amino acid changing (K-T, S-G, F-Y and F-S), respectively. And in CYP4F2 three of six SNP sites were sense, including G19026A in 3'uncoding region, T2013G and G18000A causing amino substitute (V-G and V-M) , respectively. Others were in intron region or synonymous.Conclusion This study suggests that multiple variants exist within or near the CYP4A11 and CYP4F2 genes in Chinese populations. Most of variants were nonsense or in intron region. These SNPs or variants may change biologicalactivity ofω-hydroxylases. It may provide some directions for protein research consequently.