Abstract 11339: Relationship of LPA Single Nucleotide Polymorphisms With Apolipoprotein (a) Isoforms and Biomarkers of Oxidized Lipoproteins in African-Americans, Caucasians and Hispanics: Results From the DALLAS Heart Study

Background: Oxidized phospholipids (OxPL) measured on apolipoprotein B-100 particles (OxPL-apoB) are a measure of the pro-inflammatory activity of Lp(a). Lp(a) in plasma is genetically determined by variability in kringle IV (KIV) repeats and single nucleotide polymorphisms (SNPs) in the LPA gene, is causally related to cardiovascular disease (CVD) and has become a target of therapy. Methods and Results: OxPL-apoB IgG and IgM autoantibodies to oxidized LDL and apoB-immune complexes, KIV repeats of the major apolipoprotein (a) isoform, LPA snps rs3798220, rs10455872 and rs9457951 were measured in 3454 subjects (1798 African-Americans, 1032 Caucasian and 576 Hispanic) subjects enrolled in the Dallas Heart Study (Table). All 3 snps were highly correlated with the number of KIV repeats in African-Americans but only rs3798220 and rs10455872 were correlated with KIV repeats in Caucasians or Hispanics. rs3798220 and rs10455872 demonstrated strong correlations with Lp(a) and OxPL-apoB levels in subjects with low numbers of KIV repeats, whereas rs9457951 showed similar associations only in African-Americans. None of the LPA snps correlated with the other biomarkers of oxidation. Conclusion: Significant racial differences exist among LPA SNPs and their relationship to Lp(a), apolipoprotein (a) isoforms and OxPL-apoB. These findings may provide insights into the clinical variability of Lp(a)-mediated risk in different racial groups and suggests novel avenues of investigation and therapeutic potential in mitigating the CVD risk of Lp(a) and OxPL-apoB.

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Single Nucleotide Polymorphisms in Promoter Region of Tgf-β 1 Gene Distinguish African Americans from Caucasians: A Possible Genetic Basis for Racial Differences in Epidemiology of Hypertension and End Stage Renal Disease.

Hypertension ◽

10.1161/hyp.36.suppl_1.717-d ◽

2000 ◽

Vol 36 (suppl_1) ◽

pp. 717-717

Author(s):

Ruchuang Ding ◽

Baogui Li ◽

Mohini Gulhati ◽

Yun Zhang ◽

Geraldine Helseth ◽

...

Keyword(s):

African Americans ◽

Single Nucleotide Polymorphisms ◽

Renal Disease ◽

Racial Differences ◽

End Stage Renal Disease ◽

Transforming Growth Factor ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Stage Renal Disease ◽

End Stage

P135 Transforming growth factor-beta 1 (TGF-β 1 ) excess is a candidate risk factor for hypertension and hypertensive complications including LVH, vascular remodeling and end stage renal disease (ESRD). We reported that hyperexpression of TGF-β 1 protein is more prevalent in African Americans (AA) compared with Caucasians (C), particularly AA with hypertension and/or ESRD. Single nucleotide polymorphisms (SNPs) have been reported in the TGF-β 1 gene, and there is evidence for heritable control of TGF-β 1 protein levels. In this study we tested the hypothesis that TGF-β 1 SNPs distinguish AA from C. We determined the frequencies of all 6 known biallelic TGF-β 1 DNA polymorphisms in 793 subjects (AA=342 [normal: 77, hypertension: 66, ESRD: 199], C=451 [normal: 142, hypertension: 81, ESRD: 228]). SNPs as well as cis/trans combination of alleles (haplotypes) were identified by designing and using allele specific primers in an amplification refractory mutation system PCR . Our data demonstrate that SNPs at -800bp and -509bp and the haplotype frequencies (GC, GT, AC, AT) are significantly different between AA and C (Table). In conclusion, genetically determined differences in TGF-β 1 production may explain TGF-β 1 excess in AA as well as provide a molecular basis for the excess burden of hypertension and hypertensive complications in AA.

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