Korean J Lab Med.  2010 Feb;30(1):51-57. 10.3343/kjlm.2010.30.1.51.

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

• Park HD
• Park KU
• Song J
• Ki CS
• Han KS
• Kim JQ

• KMID: 1096819
• DOI: http://doi.org/10.3343/kjlm.2010.30.1.51

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/le(59,508), and Le/le(59,1067)-accounted for 95% of the study population. In the Korean population, the allelic frequencies of Le, Le(59), le(59,508), and le(59,1067) 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/le(59,508), and Le/le(59,1067) 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.

Keyword

Lewis genotype; Lewis/Secretor genotype; CA 19-9; Korean population

MeSH Terms

Adult
Aged
Alleles
Asian Continental Ancestry Group/*genetics
CA-19-9 Antigen/*blood
Chemiluminescent Measurements/methods
Female
Gene Frequency
Genotype
Humans
Immunoassay/methods
Lewis Blood-Group System/*genetics
Male
Middle Aged
Phenotype
Polymorphism, Genetic
Republic of Korea

Figure

• 

  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.

Reference

1.Mollicone R., Reguigne I., Kelly RJ., Fletcher A., Watt J., Chatfield S, et al. Molecular basis for Lewis alpha(1,3/1,4)-fucosyltransferase gene deficiency (FUT3) found in Lewis-negative Indonesian pedigrees. J Biol Chem. 1994. 269:20987–94.

2.Nishihara S., Narimatsu H., Iwasaki H., Yazawa S., Akamatsu S., Ando T, et al. Molecular genetic analysis of the human Lewis histo-blood group system. J Biol Chem. 1994. 269:29271–8.

3.Kelly RJ., Rouquier S., Giorgi D., Lennon GG., Lowe JB. Sequence and expression of a candidate for the human Secretor blood group alpha (1,2)fucosyltransferase gene (FUT2). Homozygosity for an enzyme-inactivating nonsense mutation commonly correlates with the non-secretor phenotype. J Biol Chem. 1995. 270:4640–9.

4.Kudo T., Iwasaki H., Nishihara S., Shinya N., Ando T., Narimatsu I, et al. Molecular genetic analysis of the human Lewis histo-blood group system. II. Secretor gene inactivation by a novel single missense mutation A385T in Japanese nonsecretor individuals. J Biol Chem. 1996. 271:9830–7.

5.Koda Y., Soejima M., Liu Y., Kimura H. Molecular basis for secretor type alpha(1,2)-fucosyltransferase gene deficiency in a Japanese population: a fusion gene generated by unequal crossover responsible for the enzyme deficiency. Am J Hum Genet. 1996. 59:343–50.

6.Rouquier S., Lowe JB., Kelly RJ., Fertitta AL., Lennon GG., Giorgi D. Molecular cloning of a human genomic region containing the H blood group alpha(1,2)fucosyltransferase gene and two H locus-related DNA restriction fragments. Isolation of a candidate for the human Secretor blood group locus. J Biol Chem. 1995. 270:4632–9.

7.Liu Y., Koda Y., Soejima M., Uchida N., Kimura H. PCR analysis of Lewis-negative gene mutations and the distribution of Lewis alleles in a Japanese population. J Forensic Sci. 1996. 41:1018–21.

8.Song SY., An SS., Ryu SW., Kim JS., Suh IB. Evaluation of the genotypes of the Lewis blood group in a Korean population using direct sequencing. Korean J Hematol. 2008. 43:34–42.

9.Kim MJ., Kim HS., Song KS., Noh SH., Kim HG., Paik YK, et al. Altered expression of Lewis antigen on tissue and erythrocytes in gastric cancer patients. Yonsei Med J. 2002. 43:427–34.

10.Hayashi N., Nakamori S., Okami J., Nagano H., Dono K., Umeshita K, et al. Association between expression levels of CA 19-9 and N-acetylglucosamine-beta;1,3-galactosyltransferase 5 gene in human pancreatic cancer tissue. Pathobiology. 2004. 71:26–34.

11.Lamerz R. Role of tumour markers, cytogenetics. Ann Oncol. 1999. 10:145–9.

12.Hamajima N., Saito T., Matsuo K., Tajima K. Competitive amplification and unspecific amplification in polymerase chain reaction with confronting two-pair primers. J Mol Diagn. 2002. 4:103–7.

13.Shibata A., Hamajima N., Ikehara Y., Saito T., Matsuo K., Katsuda N, et al. ABO blood type, Lewis and Secretor genotypes, and chronic atrophic gastritis: a cross-sectional study in Japan. Gastric Cancer. 2003. 6:8–16.

14.Hamajima N., Shibata A., Ikehara Y., Katsuda N., Mori S., Ito H, et al. Lack of consistency in the associations of Helicobacter pylori sero-positivity with Se and Le polymorphisms among Japanese. Gastric Cancer. 2002. 5:194–200.

15.Park KU., Song J., Han KS., Kim JQ. The fusion allele of the FUT2 (secretor type alpha(1,2)-fucosyltransferase) gene at a high frequency and a new se385 allele in a Korean population. Ann Hematol. 2005. 84:656–60.

16.Pang H., Liu Y., Koda Y., Soejima M., Jia J., Schlaphoff T, et al. Five novel missense mutations of the Lewis gene (FUT3) in African (Xhosa) and Caucasian populations in South Africa. Hum Genet. 1998. 102:675–80.

17.Liu TC., Chang JG., Lin SF., Chang WC., Yang TY., Lin CL, et al. Lewis (FUT3) genotypes in Taiwanese, Thai, and Filipino populations. Ann Hematol. 2000. 79:599–603.

18.Liu YH., Koda Y., Soejima M., Pang H., Wang BJ., Kim DS, et al. The fusion gene at the ABO-secretor locus (FUT2): absence in Chinese populations. J Hum Genet. 1999. 44:181–4.

19.Liu Y., Koda Y., Soejima M., Pang H., Schlaphoff T., du Toit ED, et al. Extensive polymorphism of the FUT2 gene in an African (Xhosa) population of South Africa. Hum Genet. 1998. 103:204–10.

20.Narimatsu H., Iwasaki H., Nakayama F., Ikehara Y., Kudo T., Nishihara S, et al. Lewis and secretor gene dosages affect CA19-9 and DU-PAN-2 serum levels in normal individuals and colorectal cancer patients. Cancer Res. 1998. 58:512–8.

21.Vestergaard EM., Hein HO., Meyer H., Grunnet N., Jorgensen J., Wolf H, et al. Reference values and biological variation for tumor marker CA 19-9 in serum for different Lewis and secretor genotypes and evaluation of secretor and Lewis genotyping in a Caucasian population. Clin Chem. 1999. 45:54–61.

22.Liu YH., Koda Y., Soejima M., Pang H., Wang B., Kimura H. Lewis (FUT3) genotypes in two different Chinese populations. J Forensic Sci. 1999. 44:82–6.