ABSTRACT
In many studies about biomedical research factors influence on the outcome variable,it has no influence or has a positive effect within a certain range.Exceeding a certain threshold value,the size of the effect and/or orientation will change,which called threshold effect.Whether there are threshold effects in the analysis of factors (x) on the outcome variable (y),it can be observed through a smooth curve fitting to see whether there is a piecewise linear relationship.And then using segmented regression model,LRT test and Bootstrap resampling method to analyze the threshold effect.Empower Stats software developed by American X & Y Solutions Inc has a threshold effect analysis module.You can input the threshold value at a given threshold segmentation simulated data.You may not input the threshold,but determined the optimal threshold analog data by the software automatically,and calculated the threshold confidence intervals.
ABSTRACT
<p><b>BACKGROUND</b>In a previously identified locus linked to hypertension on chromosome 15q, we identified three blood pressure candidate genes: insulin-like growth factor 1 receptor gene (IGF1R), myocyte specific enhancer factor 2A gene (MEF2A), and paired basic amino acid cleaving enzyme 4 gene (PACE4). In this study, we tested their associations with hypertension using haplotype analysis.</p><p><b>METHODS</b>A total of 288 unrelated individuals, including 163 high diastolic blood pressure (DBP) subjects and 125 normal DBP subjects were enrolled in this case-control study. Twenty single nucleotide polymorphisms (SNPs) in the three genes were genotyped using polymerase chain reaction followed by restriction enzyme digestion. Haplotype analysis was accomplished in the following stages: (1) pair-wise linkage disequilibrium test among SNPs on the same gene was performed to explore blocks in which recombination is very unlikely to happen; (2) Estimation-Maximization algorithm was applied to estimate haplotype frequencies in each block; (3) the chi-square test was used to examine the specific haplotype difference, and a permutation test was used to examine the overall haplotype profile difference between cases and controls in each block.</p><p><b>RESULTS</b>An estimated haplotype "CCCCG" frequency in the haplotype block on the PACE4 gene was significantly higher in high DBP cases than in controls (P < 0.01). The overall estimated haplotype profile in this block was also significantly different between the cases and the controls (P < 0.001). This association indicates.</p><p><b>CONCLUSIONS</b>This study for the first time demonstrated that PACE4 gene may play an important role in the regulation of DBP. This association indicates that variations influencing DBP resides in or near this genomic region.</p>