Recently, an association between the presence of antibodies to Saccharomyces cerevisiae (ASCA) and mutations in exon 1 and the promoter region of the mannan binding lectin (MBL) gene was described in 58 patients with Crohn's disease (CD).1 A possible link between ASCA and MBL mutations in patients with CD is plausible. MBL is a component of the innate immune system that can bind to S cerevisiae and the serum concentration of MBL depends on structural mutations in exon 1 and promoter polymorphisms.
Table 1 Different mannan binding lectin (MBL) variants and the presence of anti‐Saccharomyces cerevisiae (ASCA).
| Prevalence of ASCA (%) | p Value (χ2 test) | Titres of ASCA (EU/ml)* | p Value (Kruskal‐Wallis or Mann‐Whitney U) | |
|---|---|---|---|---|
| MBL exon 1 | 0.62 | 0.82 | ||
| (codons 52, 54, 57) | ||||
| A/A | 54 | 4.12 (1.12‐11.88) | ||
| A/O | 58 | 4.48 (1.46‐10.18) | ||
| O/O | 67 | 5.31 (0.95‐8.23) | ||
| MBL promoter | ||||
| C‐225G | 0.61 | 0.55 | ||
| Y/Y | 55 | 4.37 (1.32‐11.81) | ||
| Y/X | 52 | 3.61 (1.05‐9.87) | ||
| X/X | 71 | 5.61 (3.25‐6.41) | ||
| MBL | 0.27 | 0.43 | ||
| Sufficient | 53 | 3.64 (1.23‐10.32) | ||
| (A/A+YA/O) | ||||
| Insufficient | 63 | 4.96 (0.92‐10.45) | ||
| (XA/O+O/O) |
*Values are median (interquartile range).
Wild‐type alleles are designated A (structural alleles) and Y (promoter −225 allele). Mutant alleles are designated O (structural alleles) and X ( promoter −225 allele).
We previously found no association between structural mutations in exon 1 of the MBL gene and susceptibility to CD.2 In view of the recent report of Seibold and colleagues,1 we were interested to see if we could confirm the reported association between ASCA and MBL mutations in a larger and independent cohort of CD patients. Three point mutations in exon 1 (codons 52, 54, and 57) and one polymorphism in the promoter region (C‐225G) of the MBL gene were genotyped using polymerase chain reaction‐restriction fragment length polymorphism or ARMS in a cohort of 241 CD patients. Statistical analysis was performed using SPSS 12.0 for Windows. The results are summarised in table1.
We found no association between the presence of ASCA and structural MBL mutations in exon 1 (codon 52, 54, and 57) (p = 0.62; χ2). Similarly, we found no association between the presence of ASCA and MBL promoter polymorphism C‐225G (p = 0.61; χ2). Furthermore, no statistical difference was found between ASCA titre and MBL structural genotypes in exon 1 (p = 0.82; Kruskal‐Wallis) and promoter polymorphism C‐225G (p = 0.55; Kruskal‐Wallis). Finally, no difference was found when we compared sufficient and insufficient MBL alleles towards either the presence or the titre of ASCA (see table1).
We found no association between the presence of ASCA and polymorphisms/mutations in the MBL gene in a large cohort of CD patients and conclude that the occurrence of ASCA is not related to MBL polymorphisms/mutations. This is in contrast with a previous report in which such an association was suggested.1 Therefore, we consider the relationship between ASCA and MBL highly controversial.
Footnotes
Conflict of interest: None declared.
References
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