Anti-A1BG monoclonal antibody, clone FQS0941(C)

The distribution of plasma alpha1B-glycoprotein (A1BG) was determined by a two-dimensional electrophoresis (agarose-polyacrylamide gel) followed by protein staining in a group of 1099 individuals from 11 populations of the Indian subcontinent. The sample comprised 454 from several tribes of Arunachal Pradesh; 76 Bengali Hundus and 88 Bengali Muslims; 179 Tamil Hindus from Singapore and 107 from India; 81 Tamil Muslims, 48 Sinhalese from Sri Lanka and 66 North Indians, Three common A1BG phenotypes (1-1, 1-2 and 2-2) were observed in this study. One each of a new allele (A1BG*7) in heterozygous form (1-7) was detected respectively among Tamil Hindus of India and Singapore. The phenotypic distribution of A1BG alleles was at Hardy-Weinberg equilibrium in all the populations. The frequency of A1BG*2 was in general lower in the Mongoloid tribes of Arunachal Pradesh (0.043-0.104) and North Indians (0.068) compared to that in other Indian populations (0.130-0.171) and Sinhalese (0.208).

We sought to identify novel pharmacogenetic markers associated with cardiovascular outcomes in patients with hypertension on antihypertensive therapy. We genotyped a 1:4 case:control cohort (n=1345) on the Illumina HumanCVD Beadchip from the INternational VErapamil SR-Trandolapril STudy (INVEST), where participants were randomized to a -blocker strategy or a calcium channel blocker strategy. Genome-spanning single nucleotide polymorphism (SNP)xtreatment interaction analyses of nonsynonymous SNPs were conducted in white and Hispanic race/ethnic groups. Top hits from whites were tested in Hispanics for consistency. A genetic risk score was constructed from the top 3 signals and tested in the Nordic Diltiazem study. SIGLEC12 rs16982743 and A1BG rs893184 had a significant interaction with treatment strategy for adverse cardiovascular outcomes (INVEST whites and Hispanics combined interaction P=0.0038 and 0.0036, respectively). A genetic risk score, including rs16982743, rs893184, and rs4525 in F5, was significantly associated with treatment-related adverse cardiovascular outcomes in whites and Hispanics from the INVEST study and in the Nordic Diltiazem study (meta-analysis interaction P=2.39x10(-5)). In patients with a genetic risk score of 0 or 1, calcium channel blocker treatment was associated with lower risk (odds ratio [95% confidence interval]=0.60 [0.42-0.86]), and in those with a genetic risk score of 2 to 3, calcium channel blocker treatment was associated with higher risk (odds ratio [95% confidence interval]=1.31 [1.08-1.59]). These results suggest that cardiovascular outcomes may differ based on SIGLEC12, A1BG, F5 genotypes, and antihypertensive treatment strategy. These specific genetic associations and our risk score provide insight into a potential approach to personalized antihypertensive treatment selection.