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Park, Park, Song, Ki, Han, and Kim: The Relationship between Lewis/Secretor Genotypes and Serum Carbohydrate Antigen 19-9 Levels in a Korean Population
Original Article

Korean J Leg Med 2010;30(1):51-57.

Published online: 14 January 2010

DOI: https://doi.org/10.3343/kjlm.2010.30.1.51

The Relationship between Lewis/Secretor Genotypes and Serum Carbohydrate Antigen 19-9 Levels in a Korean Population

Hyung-Doo Park, M.D.1, Kyoung Un Park, M.D.2, 3, Junghan Song, M.D.2, 3, Chang-Seok Ki, M.D.1, Kyou Sup Han, M.D.2, Jin Q Kim, M.D.2

1Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea

3Department of Laboratory Medicine, Seoul National University Bundang Hospital, Seongnam, Korea

Corresponding author: Kyoung Un Park, M.D. Department of Laboratory Medicine, Seoul National University Bundang Hospital, 300 Gumi-dong, Bundang-gu, Seongnam 463-707, Korea Tel: +82-31-787-7692 Fax: +82-31-787-4015 E-mail: m91w95@dreamwiz.com

      Revised 10 July 20094 August 2009       Accepted 23 September 2009

Copyright © 2010 Korean Society for Legal Medicine

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background:

The Lewis histo-blood group system consists of 2 major antigens-Lea and Leb-and a sialyl Lewis antigen-carbohydrate antigen (CA) 19-9. We investigated the distribution of Lewis genotypes and evaluated the relationship between the Lewis/Secretor genotypes and the serum level of CA 19-9 in a Korean population to identify whether the serum CA 19-9 levels are influenced by the Lewis/Secretor genotypes.

Methods:

The study included 242 individuals who had no malignancies. Lewis genotyping was performed for the 59T>G, 508G>A and 1067T>A polymorphic sites. The Secretor genotype was determined through analysis of the 357C>T and 385A>T polymorphic sites and the fusion gene. Serum CA 19-9 level was analyzed using an electrochemiluminescence immunoassay.

Results:

Individuals carrying the 3 common genotypes-Le/Le, Le/le59,508, and Le/le59,1067-accounted for 95% of the study population. In the Korean population, the allelic frequencies of Le, Le59, le59,508, and le59,1067 were 0.731, 0.010, 0.223, and 0.035, respectively. We found a significant difference in serum CA 19-9 concentrations among the 9 Lewis/Secretor genotype groups (P<0.001). The serum CA 19-9 levels in subjects with genotype groups 1 and 2 (Le/- and se/se) were higher than those with genotype groups 3-6 (Le/- and Se/-; 15.63 vs 6.64 kU/L, P<0.001).

Conclusions:

Le/Le, Le/le59,508, and Le/le59,1067 are frequent Lewis genotypes in Koreans. Because serum CA 19-9 levels are significantly influenced by the Lewis/Secretor genotypes, caution is suggested when interpreting the serum CA 19-9 levels.

Keywords: Lewis genotype, Lewis/Secretor genotype, CA 19-9, Korean population

REFERENCES

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Fig. 1.
The electrophoretic patterns of PCR-CTPP and PCR-RFLP. Lane M was a DNA size marker. (A) Determination of Lewis 59T> G genotype. Alleles T and G were characterized by amplification bands of 329 and 81 bp, respectively. A common band of 373 bp appeared for both alleles. (B) The 206 bp product was cleaved by Pvu II digestion in order to determine the Lewis 508G>A genotype. Lanes 1 and 3, GG; lanes 2 and 4, GA. (C) The second PCR product (109 bp) was cleaved by Hind III enzymatic digestion to determine the Lewis 1067T>A mutation. Lanes 1 and 3, TT; lane 2, TA. (D) The amplification products of 284 bp, 216 bp, and 353 bp represented the A, T, and fusion allele, respectively in the Secretor 385A>T genotyping. A common band of 460 bp appeared for the A and T alleles. (E) Determination of C and T alleles for the Secretor 357C>T genotype. The second PCR product (98 bp) was cleaved by Ase I digestion to confirm Secretor 357C>T genotype. Lanes 1-4, TT; lane 5, CT.
Abbreviations: PCR-CTPP, PCR with the confronting two-pair primers; PCR-RFLP, PCR and restriction fragment length polymorphism.
kjlm-30-51f1.tif
Table 1.
Primer sequences for Lewis/Secretor genotyping by PCR-RFLP
Gene Forward/reverse Primer sequence
Lewis Le59-F1 5′-CCA TGG ATC CCC TGG GTG-3′
  Le59-R1 5′-CCA CCA GCA GCT GAA ATA GCC-3′
  Le59-F2 5′-CGC TGT CTG GCC GCA CT-3′
  Le59-R2 5′-GAA GGT GGG AGG CGT GAC TTA-3′
  Le508-F 5′-ACT TGG AGC CAC CCC CTA ACT GCC A-3′
  Le508-R 5′-TGA GTC CGG CTT CCA GTT GGA CAC C-3′
  Le1067-F1 5′-CTC CCG ACA GGA CAC CAC TCC CA-3′
  Le1067-R1 5′-CTC AAG CTT CGT GCC GTG ATG ATC TCT CTG CAC-3′
  Le1067-F2 5′-CGC TCC TTC AGC TGG GCA CTG GA-3′
  Le1067-R2 5′-CGG CCT CTC AGG TGA ACC AAG AAG CT-3′
Secretor Se357-F1 5′-CTC GAA TTC GGG CCT CCA TCT CCC AGC TAA C-3′
  Se357-R1 5′-CTC AAG CTT GCT TCT CAT GCC CGG GCA CTC-3′
  Se357-F2 5′-CAG GAT CCC CTG GCA GAA CTA CCA CAT TAA-3′
  Se357-R2 5′-AGC AGG GGT AGC CGG TGA AGC GGA CGT ACT-3′
  Se385-F0 5′-TTT CAC TGC CAC CAG CAC CTG-3′
  Se385-F1 5′-ATC AAA GGC ACT GGG ACC CAG-3′
  Se385-R1 5′-GGA CGT ACT CCC CCG GGA T-3′
  Se385-F2 5′-TGG AGG AGG AAT ACC GCC ACT-3′
  Se385-R2 5′-GTC CCC TCG GCG AAC ATG G-3′
Table 2.
Distribution of Lewis genotypes in a Korean population
Genotypes Number %
Le/Le 119 49.2
Le/Le59 5 2.1
Le/le59,508 96 39.7
Le/le59,1067 15 6.2
le59,508/le59,508 6 2.5
le59,1067/le59,1067 1 0.4
Total 242 100.0
Table 3.
Comparison of Lewis allele frequencies among different populations
Allele Korean (N=242) Xhosa∗ (African) (N=100) Caucasian∗ (N=100) Japanese† (N=149) Shenyang‡ (Chinese) (N=138) Guangzhou‡ (Chinese) (N=154) Taiwanese§ (N=137)
Le 0.731 0.500 0.675 0.607 0.750 0.675 0.682
Le59 0.010 0.000 0.020 0.000 0.011 0.026 -
le59,508 0.223 0.310 0.010 0.275 0.145 0.140 -
le59,1067 0.035 0.025 0.130 0.114 0.054 0.123 -
le508 0.000 0.000 0.000 0.000 0.000 0.000 0.128
le1067 0.000 0.000 0.005 0.003 0.004 0.010 0.139
Le304 - 0.020 0.005 - - - -
Le370 - 0.005 0.000 - - - -
le202 - 0.015 0.010 - 0.000 0.000 0.000
le202,314 - 0.080 0.140 - 0.036 0.026 0.051
le202,314,484 - 0.000 0.005 - - - -
le484,667 - 0.025 0.000 - - - -
le484,667,808 - 0.020 0.000 - - - -

The allele Le indicates a functional allele and le a nonfunctional allele (-, not examined).

∗ Data from Pang et al. [16];

† Data from Liu et al. [7]

‡ Data from Liu et al. [22

§ Data from Liu et al. [17]

Table 4.
Lewis/Secretor genotype-specific values for serum CA 19-9∗
  Genotype groups N CA 19-9 (kU/L)
Lewis Secretor Median Range URL
1 Le/Le se/se 33 16.21 5.87-79.25 15.01
2 Le/le se/se 32 13.88 <0.60-35.09 48.06
3 Le/Le Se/se 88 7.13 0.78-31.03 6.65
4 Le/le Se/se 77 5.95 <0.60-27.79 18.02
5 Le/Le Se/Se 3 13.21 12.52-25.15 -
6 Le/le Se/Se 2 1.99 <0.60-3.38 -
7 le/le Se/Se 1 <0.60 - -
8 le/le Se/se 5 <0.60 - -
9 le/le se/se 1 <0.60 - -

∗ There was a significant difference in the serum CA 19-9 concentrations among the 9 genotype groups (P<0.001).

URL, Upper reference limit is the nonparametrically calculated 0.975 fractile.

Table 5.
Comparison of the serum CA 19-9 concentrations according to Lewis/Secretor genotype groups
Genotype groups∗ Genotype N CA 19-9 (kU/L)
Median Range URL
7, 8, 9 le/le and -/- 7 <0.60 - -
1, 2 Le/- and se/se 65 15.63 <0.60-79.25 36.65
3, 4, 5, 6 Le/- and Se/- 170 6.64 <0.60-31.03 20.30

∗ Genotype groups are same as in Table 1.

URL, Upper reference limit is the nonparametrically calculated 0.975 fractile.

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