title: Effects of protein coding polymorphisms in the kallikrein 1 gene on baseline blood pressure and antihypertensive response to irbesartan in Chinese hypertensive patients.
abstract: The aim of this study was to determine the association between coding variants in the human tissue kallikrein 1 (KLK1) gene and baseline blood pressure (BP) and antihypertensive response to irbesartan treatment in Chinese hypertensive patients. A total of 1061 hypertensives were recruited and received daily oral dosage of 150 mg irbesartan for 4 weeks. Predose BPs, BPs and blood irbesartan concentrations at postdose on the 28th day were all measured. Common functional single-nucleotide polymorphisms (SNPs) in the KLK1 gene were genotyped. On the basis of the HapMap data of Han Chinese in the Beijing population, two non-synonymous polymorphisms with minor allele frequency>0.1, SNP rs5517 (Glu162Lys) and rs5516 (Gln121Glu), were selected. Those with GG genotype in the rs5516 locus had higher average baseline systolic BP (SBP) than CC subjects (β±s.e.: 5.0±2.3, P=0.033); and no associations of rs5517 with baseline BP (diastolic BP (DBP) and SBP) and BP responses, or rs5516 with baseline DBP and BP response were observed. In a haplotype-based association test for the KLK1 gene, the Haplo-special score analyses identified that haplotype AG was marginally associated with SBP response (specific score: 1.75 for P=0.08), but not with DBP response. We did not find any associations between haplotypes (GC and AC) and BP responses. The Haplo-GLM analyses showed that, compared with haplotype GC subjects, the subjects with haplotype AG had a marginally greater SBP response (adjusted β±s.e.: 1.81±0.97, P=0.06), but DBP response did not differ. This study suggests that rs5516 in the KLK1 gene may be involved in the development of essential hypertension and in the regulation of SBP-lowering response to irbesartan in Chinese hypertensives.
authors.affiliation: School of Life Sciences, Anhui University, Hefei, China. shanqun@gmail.com
authors.forename: S
authors.initials: S
authors.lastname: Jiang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Hsu
authors.forename: S A
authors.initials: SA
authors.lastname: Venners
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Xing
authors.forename: X
authors.initials: X
authors.lastname: Wang
authors.forename: X
authors.initials: X
authors.lastname: Xu
mesh_terms: D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use*; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D044466:Asian People; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000209:etiology / Q000235:genetics*; D000077405:Irbesartan; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D013777:Tetrazoles / Q000627:therapeutic use*; D020840:Tissue Kallikreins / Q000235:genetics*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D013777:Tetrazoles; D020840:Tissue Kallikreins; D000077405:Irbesartan