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Apolipoprotein A polymorphisms and plasma lipoprotein(a) concentrations in non-Hispanic Whites and Hispanics
L Chiu1, R F Hamman, M I Kamboh
1Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, PA 15261, USA.
Elevated levels of plasma lipoprotein(a) [Lp(a)] are thought to be a risk factor for atherosclerosis and coronary heart disease. Plasma levels of Lp(a) are highly variable between individuals, ranging from 0.1 mg/dL to > 100 mg/dL These levels are under strict genetic control, and genetic variation in the apolipoprotein A (APOA) gene accounts for almost all variation in Lp(a) levels. In this study, we investigated the relationship between two APOA polymorphisms (kringle 4 and 5' pentanucleotide repeat) and plasma Lp(a) levels in normoglycemic non-Hispanic Whites (NHWs) (n = 390) and Hispanics (n = 214) from the San Luis Valley, Colorado. Mean (+/- SD) and median Lp(a) levels were 9.6 +/- 12.5 mg/dL and 3.8 mg/dL, respectively, in NHWs and 12.1 +/- 15.6 mg/dL and 4.9 mg/dL, respectively, in Hispanics. The number of observed kringle 4 repeats ranged from 11 to 38 in NHWs and from 10 to 41 in Hispanics. Spearman rank correlation revealed an inverse relationship between the size of the kringle 4 repeat and plasma Lp(a) levels in both populations (r = -0.38; p < 0.0001 in NHWs and r = -0.64; p < 0.0001 in Hispanics). About 30% and 48% of the variation in plasma Lp(a) was explained by this polymorphism in NHWs and Hispanics, respectively. This study confirms that the kringle 4 polymorphism in the APOA gene is a significant determinant of Lp(a) levels in both study groups. A pentanucleotide repeat polymorphism in the 5' promoter region of the APOA gene did not show significant impact on plasma Lp(a) levels in either NHWs or Hispanics.
Elevated levels of plasma lipoprotein(a) [Lp(a)] are thought to be a risk factor for atherosclerosis and coronary heart disease. Plasma levels of Lp(a) are highly variable between individuals, ranging from 0.1 mg/dL to > 100 mg/dL These levels are under strict genetic control, and genetic variation in the apolipoprotein A (APOA) gene accounts for almost all variation in Lp(a) levels. In this study, we investigated the relationship between two APOA polymorphisms (kringle 4 and 5' pentanucleotide repeat) and plasma Lp(a) levels in normoglycemic non-Hispanic Whites (NHWs) (n = 390) and Hispanics (n = 214) from the San Luis Valley, Colorado. Mean (+/- SD) and median Lp(a) levels were 9.6 +/- 12.5 mg/dL and 3.8 mg/dL, respectively, in NHWs and 12.1 +/- 15.6 mg/dL and 4.9 mg/dL, respectively, in Hispanics. The number of observed kringle 4 repeats ranged from 11 to 38 in NHWs and from 10 to 41 in Hispanics. Spearman rank correlation revealed an inverse relationship between the size of the kringle 4 repeat and plasma Lp(a) levels in both populations (r = -0.38; p < 0.0001 in NHWs and r = -0.64; p < 0.0001 in Hispanics). About 30% and 48% of the variation in plasma Lp(a) was explained by this polymorphism in NHWs and Hispanics, respectively. This study confirms that the kringle 4 polymorphism in the APOA gene is a significant determinant of Lp(a) levels in both study groups. A pentanucleotide repeat polymorphism in the 5' promoter region of the APOA gene did not show significant impact on plasma Lp(a) levels in either NHWs or Hispanics.