Short mucin 1 alleles are associated with low virulent H pylori strains infection

Abstract

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TO THE EDITOR

We read with interest the article published by Nguyen et al[1] in the World Journal of Gastroenterology, showing an association between short MUC6 alleles and H pylori infection. These results, together with previous observations by Vinall et al[2], reinforce the role of mucin genes (MUC6 and MUC1) VNTR polymorphisms for the variability in individual susceptibility to H pylori infection that cannot be explained by differences in environmental factors.

We conducted a similar analysis based on a previously described[3] survey of gastric pathology in shipyard workers at Viana do Castelo, north of Portugal. Briefly, volunteer workers underwent an upper digestive endoscopy, completed symptoms and lifestyle questionnaires, and had a blood sample drawn. H pylori infection status was determined by serology and PCR, and typing of cagA, vacA s and vacA m was performed directly in gastric biopsy specimens by multiplex PCR and reverse hybridization[4]. The MUC1 gene polymorphisms were evaluated by Southern blot analysis[5].

Information on MUC1 genotypes and H pylori infection status was available for 216 subjects (median age: 43 years; 91% males). For analysis, each participant was considered infected if positive by either serology or PCR (n = 172, 79.6%), and classified according to MUC1 genotype [long-long (LL), long-short (LS), short-short (SS)]. Data on H pylori genotypes were available for 161 participants. The association between MUC1 genotypes and H pylori infection was quantified through the calculation of odds ratios (OR) and the respective 95% confidence intervals (CI) by unconditional logistic regression using STATA^®, version 9.2.

Short MUC1 alleles were associated with H pylori infection (SS vs LL: OR = 2.7, 95%CI: 1.0-7.1; LS vs LL: OR = 1.6, 95% CI: 0.7-3.7). The risk of infection (SS vs LL) was increased nearly three-fold for low-virulent strains (cagA^-, vacA s₂ or vacA m₂) and less than two-fold when considering high-virulent H pylori strains (Table 1).

Table 1 Association between MUC1 polymorphisms and H pylori infection according to bacterial genotype.

		H pylori positive
		cagA genotypes				vacA s genotypes				vacA m genotypes
	H pylori negative	cagA-	OR	cagA+	OR	s2	OR	s1 or s1/s2	OR	m2	OR	m1 or m1/m2	OR
	n (%)	n (%)	(95% CI)	n (%)	(95% CI)		(95% CI)	n (%)	(95% CI)	n (%)	(95% CI)	n (%)	(95% CI)
MUC1 genotypes
LL	10	8	1	21	1	5	1	24	1	8	1	21	1
	(25.6)	(20.5)	[reference]	(53.8)	[reference]	(12.8)	[reference]	(61.6)	[reference]	(20.5)	[reference]	(53.9)	[reference]
LS	25	30	1.5	47	0.9	24	1.9	53	0.9	34	1.7	43	0.8
	(24.5)	(29.4)	(0.5-4.4)	(46.1)	(0.4-2.2)	(23.5)	(0.6-6.4)	(52.0)	(0.4-2.1)	(33.3)	(0.6-4.9)	(42.2)	(0.3-2.0)
SS	9	22	3.1	33	1.8	16	3.6	39	1.8	23	3.2	32	1.7
	(14.1)	(34.4)	(0.9-10.2)	(51.6)	(0.6-5.0)	(25.0)	(0.9-13.7)	(61.0)	(0.6-5.1)	(35.9)	(1.0-10.7)	(50.0)	(0.6-4.9)

LL: long-long; LS: long-short; SS: short-short; OR: odds ratio CI: confidence interval.

The present study, performed in a population at high risk for gastric cancer, confirms earlier findings on the effect of mucin genes VNTR variability on H pylori infection, and adds to previous investigations the evidence of a stronger association between the short mucin alleles and low-virulent strains. However, an increased risk of infection also with high virulence strains cannot be excluded and may be shown in investigations with larger sample sizes, powered enough to disclose an association of this magnitude.

Our results are compatible with previous findings of an increased risk for both intestinal metaplasia[5] and gastric carcinoma[6] in individuals with short MUC1 mucin alleles, but additional studies should explore the combined effect of H pylori genotypes and mucin genes polymorphism on the infection outcome.

ACKNOWLEDGMENTS

Grants from the Fundação Calouste Gulbenkian (projects FC-54918 and FC-68697) and Fundação para a Ciência e a Tecnologia (JNICT UI & D 51/94, Pocti/SAU-IMI/56895/2004 and Pocti/CBO/44812/2002) are gratefully acknowledged.