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Articles by W. H. L Kao
Total Records ( 2 ) for W. H. L Kao
  Y. C Cheng , W. H. L Kao , B. D Mitchell , J. R O'Connell , H Shen , P. F McArdle , Q Gibson , K. A Ryan , A. R Shuldiner and T. I. Pollin
 

Background— Matrix metalloproteinase (MMP)-1 may play a role in cardiovascular disease susceptibility by influencing plaque rupture via its ability to degrade extracellular collagens.

Methods and Results— We performed a genome-wide association analysis of circulating MMP-1 levels using 500 K single-nucleotide polymorphisms (SNPs) to identify genes influencing variation in serum MMP-1 levels in 778 healthy Amish adults. Serum MMP-1 levels, logarithm transformed, and adjusted for age and sex, were screened for association with SNPs using mixed-model variance components to account for familial relatedness. Median MMP-1 level was 3.05 ng/mL (interquartile range: 1.82 to 5.04 ng/mL) with an estimated heritability of 81% (P<0.0001). Serum MMP-1 levels were strongly associated with a cluster of 179 SNPs extending over an 11.5-megabase region on chromosome 11q. The peak association was with rs495366 (P=5.73x10–34), located within the region between MMP-1 and MMP-3 and having a minor allele frequency of 0.36. Two other SNPs within the 11q region, rs12289128 and rs11226373, were strongly associated with MMP-1 levels after accounting for rs495366 (P≤10–7). These 3 SNPs explained 31% of the variance in MMP-1 levels after adjusting for age and sex.

Conclusions— This study provides strong evidence that the serum MMP-1 level is highly heritable and that SNPs near MMPs on chromosome 11q explain a significant portion of the variation in MMP-1 levels. Identification of the genetic variants that influence MMP-1 levels may provide insights into genetic mechanisms of cardiovascular disease.

  A. C Naj , M West , S. S Rich , W Post , W. H. L Kao , B. A Wasserman , D. M Herrington and A. Rodriguez
 

Background— Little is known about the association of scavenger receptor class B type I (SCARB1) single-nucleotide polymorphisms (SNPs) and subclinical atherosclerosis, particularly in subjects of different racial/ethnic backgrounds. We examined this relationship in the Multi-Ethnic Study of Atherosclerosis.

Methods and Results— Forty-three SCARB1-tagging SNPs were genotyped. Baseline examinations included fasting lipids and subclinical atherosclerosis phenotypes (coronary artery calcification, common carotid intimal-medial artery thickness [CCIMT], and internal carotid intimal-medial artery thickness). Examining SNP associations with different subclinical atherosclerosis phenotypes across multiple racial/ethnic groups with adjustment for multiple covariates, we found that the C allele of SNP rs10846744 was associated with higher CCIMT in African American (P=0.03), Chinese (P=0.02), European American (P=0.05), and Hispanic participants (P=0.03) and was strongly associated in pooled analyses (P=0.0002). The results also showed that the association of this SNP with CCIMT was independent of lipids and other well-established cardiovascular risk factors. Stratifying by sex, there seemed to be a strong association of rs10846744 with CCIMT in women, but no genotype-sex interactions were observed.

Conclusions— Variation in SCARB1 at rs10846744 was significantly associated with CCIMT across racial/ethnic groups in Multi-Ethnic Study of Atherosclerosis.

 
 
 
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