APOLIPOPROTEIN(a) POLYMORPHISMS IN A HEALTHY MACEDONIAN POPULATION
Tosheska K*, Labudovic D, Alabakovska S, Todorova B
*Corresponding Author: Katerina Tosheska K, MD, MSc., Department of Medical and Experimental Biochemistry, Faculty of Medicine, 50 Divizija 6, 1000 Skopje, Republic of Macedonia; Tel: +389-2-3217-303; Fax: +389-2-3230-431; E-mail: tosheskatrajkovska@yahoo.com
page: 49

RESULTS

Five apo(a) isoforms (B, S1, S3, S4 and >S4) were resolvable by the SDS-PAGE system followed by immu­noblotting with a sheep polyclonal anti-human apo(a) antibody. In each plasma, one of these five bands was generally present, either alone (single-banded phenotype) or in combination with another band (double-banded phenotype). The phenotype was defined as “null” when there were no detectable apo(a) bands.
The frequency of apo(a) phenotypes in the test subjects is shown in Table 1. One hundred and seven (59.44%) had single-banded phenotypes and 64 (35.56%) had double-banded phenotypes. Nine individuals (5%) had the “null” phenotype. There was no significant difference in the apo(a) isoform frequency distribution between gender groups (P2 = 0.514, p = 0.77).
All five of the possible single-banded phenotypes and eight of the 12 possible double-banded phenotypes were detected. The frequencies of single-banded and double-banded phenotypes are given in Table 2. Among the single-banded phenotypes, S4 was the most frequent (49.14%) and S1 and B were comparatively rare (1.72%). The S4/S3 phenotype was the most frequent (43.75%) among the double-banded phenotypes.
Based upon the hypothesis that the apo(a) polymorphism is controlled by different alleles at a single locus, the frequencies of the six alleles were: LpB = 0.022, LpS1 = 0.028, LpS3 = 0.201, LpS4&nbsp;= 0.397, Lp>S4 =0.110, and LpO = 242. Comparison of the observed phenotype frequencies with those expected from the genetic hypothesis, and assuming that the Hardy-Weinberg equilibrium showed no significant difference [P2 =17.21, degrees of freedom (df) = 15, p <0.3067) (Table 2).


As shown in Figure 1, the distribution of Lp(a) concentration is highly skewed towards lower concentrations with most of the subjects, 164 (91.1%) having an Lp(a) level beneath the cut-off point of 30 mg/dL. The plasma level of Lp(a) in males and females is presented in Ta­ble 3. There was no significant difference in plasma Lp(a) levels between the sexes (two-sample unpaired Student’s t-test, p = 0.4246). The Mr of apo(a) isoforms and Lp(a) concentrations are presented in Table 4. We confirmed that low Mr isoforms (B, S1) are associated with elevated Lp(a) concentrations, whereas the high Mr isoforms (S4 and S3) are associated with lower Lp(a) levels. We found a significant inverse correlation [Pearson’s correlation coefficient (r) = –0.3477, p <0.001) between the Mr of apo(a) isoforms and plasma levels of Lp(a) (Fig. 2).

Table 1. Frequency of apo(a) phenotypes in 180 Macedonian blood donors

 

Isoform

Males

Females

Total

 

n

%

n

%

n

%

Single

58

61.10

49

56.98

107

59.44

Double

32

 

Table 2. Frequency of observed and expected phenotypes in 180 Macedonian blood donors

 

Isoform

Observed Apo(a) Isoform

Expected Apo(a) Isoform

Single

n

%

n

%

>S4

14

12.07

11,767

10.27

S4

57

49.14

62,804

54.81

S3

32

27.59

24,810

21.65

S1

2

1.72

2591

2.26

B

2

1.72

2,050

1.79

Null

9

7.76

10,565

9.22

Total

116

100.00

114,597

100.00

Double

n

%

n

%

>S4/S4

22

34.38

15,683

23.92

>S4/S3

1

1.56

7,959

12.14

>S4/S1

0

0.00

1,112

1.70

S4/S3

28

43.75

28,673

43.75

S4/S1

6

9.38

4,005

6.11

>S4/B

0

0.00

889

1.36

S4/B

4

6.25

3,204

4.89

S3/S1

1

1.56

2,032

3.10

S3/B

1

1.56

1,626

2.48

S1/B

1

1.56

352

0.54

Total

64

100.00

65,535

100.00

 

Figure 1. Frequency distribution of Lp(a) concentration

Figure 2. Correlation between Mr of apo(a) isoforms and Lp(a) concentration.

 




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