Mannose‐binding lectin gene polymorphism and resistance to therapy in women with recurrent vulvovaginal candidiasis

Abstract

Precis Women with recurrent vulvovaginal candidiasis (RVC) due to a polymorphism in codon 54 of the MBL2 gene respond better to fluconazole maintenance therapy than do women with other underlying causes.Objective To explain differences in response rates to maintenance therapy with fluconazole in women suffering from RVC by evaluating associations with a polymorphism in the gene coding for mannose-binding lectin (MBL).Design Follow-up study, neted case-control group.Setting Women attending vulvoginitis clinic for RVC.Population Women participating in a multicentric study in Belgium with a degressive dose of fluconazole for RVC (the ReCiDiF trial) were divided into good responders, intermediate responders and nonresponders according to the number of relapses they experienced during therapy. From 109 of these women with adequate follow-up data, vaginal lavage with 2 ml of saline were performed at the moment of a proven acute attack at inclusion in the study, before maintenance treatment was started. A buccal swab was obtained from 55 age-matched women without a history of Candida infections, serving as a control group.Methods Extracted DNA from buccal or vaginal cells was tested for codon 54 MBL2 gene polymorphism by polymerase chain reaction and endonuclease digestion.Main outcome measures Frequency of MBL2 condon 54 allele B in women with optimal or poor response to maintenance therapy in composition with controls.Results Women (n = 109) suffering from RVC were more likely to carry the variant MBL2 codon 54 allele B than control women (20 versus 6.6%, OR 3.4 [95% CI 1.3-8.2], P = 0.01). B alleles were present in 25% of the 36 women not suffering from any recurrence during the maintenance therapy with decreasing doses of fluconazole (OR 4.9 [95% CI 1.9-12.5], P = 0.0007 versus controls), in 20% of the 43 women with sporadic recurrences (OR 3.6 [95% CI 1.4-9.2], P = 0.007 versus controls) and in 15% of the 30 women who had to interrupt the treatment regimen due to frequent relapses (P = 0.097 versus controls).Conclusions The MBL2 codon 54 gene polymorphism is more frequent in Belgian women suffering from RVC than in controls. The presence of the B allele is associated with a superior response to fluconazole maintenance therapy as compared with RVC patients without this polymorphism. We conclude that RVC due to deficient MBL production is more easily helped with antifungal medication than is RVC due to some other mechanism.

Infections of People with Complement Deficiencies and Patients Who Have Undergone Splenectomy

“…Because mannan is an important component of fungal cell walls, the possible role of MBL in fungal infections has been investigated. Belgian women suffering from recurrent vulvovaginal candidiasis were more likely to possess the variant mbl2 codon 54 (allele B) than control women (20 versus 6.6%; P ϭ 0.01) (97). Those authors also reported that the presence of the B allele was associated with significantly fewer recurrences among women who were placed on chronic fluconazole maintenance therapy.…”

Management of Recurrent Vulvo-Vaginal Candidosis as a Chronic Illness

“…The presence of a single nucleotide guanine 1 adenine polymorphism in codon 54 of the MBL gene has been associated with lowered vaginal concentrations of MBL protein and an increased occurrence of recurrent RVC in Latvian, Brazilian and Belgian women [45][46][47] . When the women in the ReCiDiF study were compared with normal, noninfected control women, the RVC patients were less likely to be homozygous for the wild-type AA genotype (87 vs. 63%, p = 0.0017) [46] .…”

“…When the women in the ReCiDiF study were compared with normal, noninfected control women, the RVC patients were less likely to be homozygous for the wild-type AA genotype (87 vs. 63%, p = 0.0017) [46] . The AB heterozygous genotype was almost 3 times more frequent in the RVC patients than in controls (33.0 vs. 13%, p = 0.005), while the B,B homozygous genotype was found only in RVC patients.…”

Structure, Function, Molecular Genetics, Disease Associations and Therapeutic Potential of Mannose Binding Lectin: Review

“…Vul vo va ji nal kan di di a zis dün ya da mil yon larca ka dı nı et ki le yen bir in fek si yon dur ve tek rar layan in fek si yon lu ka dın la rın %5'inin yıl da en az dört kez kan di di a zis ge çir di ği be lir len miş tir. 77,78 MBL mu tant al le li ni ta şı yan ka dın lar vul vo va ji nal kan di di a sis sen dro mu için yük sek risk gru bu na girmek te dir. 78,79 Tek rar la yan vul vo va ji nal kan di di asis li ka dın la rın ser vi ko va ji nal la vaj sı vı sın da, kon trol gru bu na gö re MBL dü zey le ri nin an lam lı de re ce de dü şük, MBL mu tas yon sık lı ğı nın ise yük-sek ol du ğu gös te ril miş tir.…”

“…77,78 MBL mu tant al le li ni ta şı yan ka dın lar vul vo va ji nal kan di di a sis sen dro mu için yük sek risk gru bu na girmek te dir. 78,79 Tek rar la yan vul vo va ji nal kan di di asis li ka dın la rın ser vi ko va ji nal la vaj sı vı sın da, kon trol gru bu na gö re MBL dü zey le ri nin an lam lı de re ce de dü şük, MBL mu tas yon sık lı ğı nın ise yük-sek ol du ğu gös te ril miş tir. 80,81 He li co bac ter pylo ri in fek si yo nu nun pep tik ül -ser ve gas trik kan ser le iliş ki li ol du ğu bi lin mek tedir.…”