Oksana Babula

Relation between Recurrent Vulvovaginal Candidiasis, Vaginal Concentrations of Mannose-Binding Lectin, and a Mannose-Binding Lectin Gene Polymorphism in Latvian Women

Vaginal concentrations of mannose-binding lectin (MBL) and possession of a polymorphism in codon 54 of the MBL gene were determined in 42 women with recurrent vulvovaginal candidiasis (RVVC) and 43 control subjects. Reduced vaginal MBL levels and an increased occurrence of the polymorphism were present in women with RVVC.

Frequency of interleukin-4 (IL-4) -589 gene polymorphism and vaginal concentrations of IL-4, nitric oxide, and mannose-binding lectin in women with recurrent vulvovaginal candidiasis

BACKGROUND A C-->T substitution at position -589 in the interleukin-4 (IL-4) gene is associated with increased production of IL-4. Associations between this polymorphism and recurrent vulvovaginal candidiasis (RVVC), as well as vaginal concentrations of IL-4 and the anticandidal compounds nitric oxide (NO) and mannose binding lectin (MBL), were evaluated. METHODS Vaginal samples obtained by lavage from 42 women with RVVC during the acute stage of the disease and 43 control samples were assayed by enzyme-linked immunosorbent assay for IL-4 and NO metabolites. The -589 IL-4 gene polymorphism was detected by polymerase chain reaction and endonuclease digestion. Data were analyzed by Fishers exact test, the nonparametric Mann-Whitney and Kruskal-Wallis tests, and Spearman rank correlation. P < .05 was considered significant. RESULTS Candida albicans was identified in 38 patients with RVVC; 3 others had infection due to Candida tropicalis, and 1 had infection due to Candida krusei. The IL-4 T,T genotype was detected in 59.5% of patients with RVVC and in 7.0% of control subjects (P < .0001). The frequency of IL-4*T was 76.2% in patients with RVVC and 23.3% in control subjects (P < .0001). The median concentration of vaginal IL-4 was elevated in patients with RVVC, compared with control subjects (P < .0001). Conversely, vaginal concentrations of NO metabolites (P = .02) and MBL (P < .0001) were reduced in patients with RVVC. There was a positive association between IL-4*T homozygosity and vaginal IL-4 levels (P < .0001) and negative associations between this genotype and vaginal NO (P = .01) and MBL (P < .0001) concentrations. CONCLUSIONS Reduced vaginal levels of anticandidal factors in IL-4*T homozygotes may increase susceptibility to RVVC.

Mannose-binding lectin gene polymorphism, vulvovaginal candidiasis, and bacterial vaginosis.

OBJECTIVE: To evaluate associations between polymorphisms in the gene coding for mannose-binding lectin (MBL) and the diagnosis of acute or recurrent vulvovaginal candidiasis and bacterial vaginosis METHODS: Women at two outpatient clinics in Brazil filled out a questionnaire and were examined for the presence of vulvovaginal candidiasis or bacterial vaginosis. A buccal swab was blindly tested for codons 54 and 57 MBL2 gene polymorphisms by polymerase chain reaction and endonuclease digestion. RESULTS: A total of 177 women were enrolled. Vulvovaginal candidiasis was identified in 78 (44.1%) women, 33 (18.6%) had bacterial vaginosis, and 66 (37.3%) were normal controls. Recurrent vulvovaginal candidiasis was present in 50 (64.1%) of the women with vulvovaginal candidiasis; 20 (60.6%) of the bacterial vaginosis patients had recurrent disease. Vulvovaginal candidiasis was associated with white race (P=.007), bacterial vaginosis was associated with nonwhite race (P=.05), and both were associated with a history of allergy (P≤.02) and having sexual intercourse at least three times a week (P<.001). Carriage of the variant MBL2 codon 54 allele B was more frequent in women with recurrent vulvovaginal candidiasis (25.0%) than in the women with acute vulvovaginal candidiasis (17.9%) or controls (10.6%) (P=.004). Allele B was also more prevalent in women with recurrent bacterial vaginosis (22.5%) than in those with acute bacterial vaginosis (0%) (P=.009). The MBL2 codon 57 polymorphism was infrequent and not associated with vulvovaginal candidiasis or bacterial vaginosis. CONCLUSION: The incidence of vulvovaginal candidiasis and bacterial vaginosis differs by ethnicity in Brazilian women. The MBL2 codon 54 gene polymorphism is associated with both recurrent vulvovaginal candidiasis and recurrent bacterial vaginosis. LEVEL OF EVIDENCE: III

Ethnic differences of polymorphisms in cytokine and innate immune system genes in pregnant women

OBJECTIVE: Investigations of the possible role of polymorphic genes in pregnancy outcome may be influenced by ethnic variations in genotype or allele frequencies. Differences in allelic carriage of immune system-related genes among white, black, and Hispanic pregnant women living in New York City and Boston were evaluated. METHODS: DNA was extracted from buccal or vaginal epithelial cells collected from 198 white, 75 black, and 114 Hispanic pregnant women who delivered at term and who had no history of a preterm birth. Genetic polymorphisms in the immunoregulatory genes encoding interleukin (IL)-1β, tumor necrosis factor-α, IL-4, IL-10, IL-1 receptor antagonist (IL-1ra), mannose-binding lectin, toll-like receptor-4, and the 70-kDa heat shock protein were determined. RESULTS: Allele 2 of the IL-1ra gene (IL1RN*2) and IL-4 –590C homozygosity were 4-fold less common in blacks than in whites or Hispanics (P < .001). The IL-4 −590T allele was almost 2-fold more common in Hispanics than in whites (P < .001). The frequency of the 70-kDa heat shock protein 1267G allele was at least 1.4 times greater in blacks compared with whites (P < .001) or Hispanics (P = .002), whereas the homozygous mannose-binding lectin codon 54G allele was observed at least 4.5 times more often in Hispanics compared with whites (P = .007) or blacks (P = .02). CONCLUSION: Investigations of the role of genetic factors affecting pregnancy outcome must be cognizant of ethnic variations when enrolling case and control subjects for studies on allele and genotype frequencies. LEVEL OF EVIDENCE: III

Association between primary vulvar vestibulitis syndrome, defective induction of tumor necrosis factor-α, and carriage of the mannose-binding lectin codon 54 gene polymorphism

OBJECTIVE We evaluated whether women with vulvar vestibulitis syndrome (VVS) could be subdivided on the basis of genotyping the polymorphic mannose-binding lectin (MBL) gene. STUDY DESIGN DNA from 123 women with VVS was tested for a single nucleotide polymorphism at codon 54 of the MBL gene. Blood samples from 86 of the women were evaluated for ex vivo tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 receptor antagonist (IL-1ra) production in response to Candida albicans, gram-positive peptidoglycan, and gram-negative lipopolysaccharide. Associations between laboratory findings and clinical characteristics were analyzed. RESULTS The variant MBL*B allele was identified in 33 subjects (26.8%). This polymorphism was more prevalent in women whose symptoms developed at their first act of sexual intercourse (primary VVS, 40.9%), as opposed to women with secondary VVS (16.3%; P = .01). Ex vivo TNF-alpha production, but not IL-1ra production, was reduced in MBL*B carriers as compared with MBL*A homozygotes (P < or = .03). CONCLUSION The MBL gene polymorphism is associated with the development of primary VVS and a reduced capacity for TNF-alpha production in response to microbial components.

Innate immune system gene polymorphisms in maternal and child genotype and risk of preterm delivery

Abstract Objective. There is little information about the combination of genetic variability in pregnant women and their children in relation to the risk of preterm delivery (PTD). In a sub-cohort of 487 non-Hispanic white and 288 African-American mother/child pairs, the Pregnancy Outcomes and Community Health Study assessed 10 functional polymorphisms in 9 genes involved in innate immune function. Methods. Race-stratified weighted logistic regression models were used to calculate odds ratios for genotype and PTD/PTD subtypes. Polymorphisms significantly associated with PTD/PTD subtypes were tested for mother/child genotype interactions. Results. Three maternal polymorphisms (IL-1 receptor antagonist intron two repeat (IL-1RN), matrix metalloproteinase- −C1562T, and TNF receptor two M196R (TNFR2)) and three child polymorphisms (IL1-RN, tumor necrosis factor-alpha −G308A, and TNFR2) were associated with PTD, but associations varied by PTD subtype and race. Two interactions were detected for maternal and child genotype. Among non-Hispanic white women, the odds of PTD was higher when both mother and child carried the IL-1RN allele two (additive interaction p < 0.05). Among African-American women, the odds of PTD were higher when both mother and child carried the TNFR2 R allele (multiplicative interaction p < 0.05). Conclusion. These results highlight the importance of assessing both maternal and child genotype in relation to PTD risk.