Y Saijo et al. 17994-revised
CapsuleThere was a statistically significant difference in the IL-6-634C→G genotype frequency between Japanese patients with recurrent pregnancy loss (RPL) and controls.Patients who carry the -634 G allele may have a decreased risk of RPL.
Y Saijo et al. 17994-revised
Structured AbstractObjective: To investigate the relationships between recurrent pregnancy loss (RPL) and single nucleotide polymorphisms (-634 C→G and -174 G→C genotypes) in the promoter region of the IL-6 gene in the Japanese population.Design: A case-control study.
Setting: Department of Obstetrics and Gynecology in a university hospital.Patient(s): 76 cases with RPL. Controls were 93 fertile women.
Intervention(s):Frequency and distribution of the promoter region of the IL-6 gene allele.
Main Outcome Measure(s): Determination of IL-6 promoter gene polymorphisms was performed by polymerase chain reaction and gel electrophoresisResults: There was a significant difference in the -634C→G genotype frequency (CC vs. CG/GG) between the women with RPL and the controls. The risk of RPL was lower in the carrier of the G allele than in women with the wild type(CC), with OR = 0.46 (95% CI = 0.24-0.91). On the other hand, we did not detect any carrier of -174C in the 169 subjects.
Conclusion(s):The results suggest that women carrying the -634 G allele of the IL-6 gene may have a decreased risk of RPL in the Japanese population. A shift to type-2 T-helper (Th2) cytokine production with abundant interleukine (IL)-6 and IL-10 is considered essential for the maintenance of normal pregnancy. There is evidence of a diminished Th2 immune response to placental antigens in women with RLP (5). Plasma levels of IL-6, IL-8 and IL-11 have been found to be decreased in such women compared with normal pregnancies (6).Additionally, IL-6 levels in maternal serum (7), amniotic fluid (8), vaginal fluid (9), and placenta (10) have been found to increase during the process of normal labor compared to the nonlabor state.One study demonstrated an increase in the frequencies of type-1 T-helper (Th1) cytokine IL-1β gene promoter region variants IL-1B-511C and IL-1B-31T in RPL women with RLP (11). One of the Th2 cytokines, IL-10 promoter region variant (-1082G→A) was not associated with RPL (12,13). However, relationships between many diseases and IL-6 promoter gene polymorphisms, such as IL-6 -174G→C (14, 15) and IL-6 -634C→G (16), were recently demonstrated. It is also known that the former polymorphism is frequently found in Caucasians (14, 15) and the latter in Japanese (16). There have been no reports of other frequent polymorphisms of the IL-6 gene, and the relationship between any IL-6 gene polymorphism and RPL has not yet been investigated. In the present study, therefore, we assessed these two promoter polymorphisms and investigated whether either of these IL-6 gene polymorphisms
Materials and MethodsThis case-control study was performed in Sapporo, Japan, during the years 1999-2002. We studied 76 cases aged 20-42 years with a history of RP...