Single nucleotide polymorphisms in the promoter region of the interleukin-6 gene and the risk of recurrent pregnancy loss in japanese women

Abstract

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...

Genetic regulation of recurrent spontaneous abortion in humans

“…[98] However, this study was contradicted by Saijo and coworkers who discovered a protector effect of GG genotypes at the −634C-->G promoter polymorphism of IL-6 in the Japanese population. [99] This association was confirmed in a Chinese sample of 162 RSA patients and 156 controls. [100] The same study did not find significant differences in IL-1β-31T, -511T, and + 3954T between RSA patients and controls.…”

Association between IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms and susceptibility to recurrent pregnancy loss: a meta-analysis

“…The reason behind this disparity between ethnic groups is unclear but may be due in part to the frequency at which these polymorphisms are present in each population. For example, the IL-6 −174 C allele has not been observed in Japanese subjects [19] and is known to be rare in Chinese and Korean populations [40,41], while this allele is common in Caucasians. The studies in Korean and Chinese populations did not examine other alleles that may be associated with RPL [40,41], but the study in Japanese population has shown that women carrying the −634G allele of the IL-6 gene have a decreased risk of RPL [19].…”

“…For example, the IL-6 −174 C allele has not been observed in Japanese subjects [19] and is known to be rare in Chinese and Korean populations [40,41], while this allele is common in Caucasians. The studies in Korean and Chinese populations did not examine other alleles that may be associated with RPL [40,41], but the study in Japanese population has shown that women carrying the −634G allele of the IL-6 gene have a decreased risk of RPL [19]. In addition, the IL-6 −634 C allele is not widespread in Middle Eastern groups [22] but is prevalent among Asians [23], a population in which the IFN-γ + 874 AA genotype is also more common compared to other non-Caucasians [17].…”

“…Subsequently, three documents were excluded for being review articles [37][38][39]. Thus, 15 relevant studies met the inclusion criteria [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]), of which, eight were related to the IL-6 −174 G/C polymorphism and involved 859 patients and 1018 controls, four concerned the IL-6 −634 G/C polymorphism and included 343 patients and 340 controls, while six referred to the IFN-γ +874 A/T polymorphism and comprised 622 patients and 712 controls (Table 1).…”

“…Based on their functional significance, the roles of IL-6 −174 G/C, IL-6 −634 G/C, and IFN-γ +874 A/T polymorphisms in RPL susceptibility have been examined, with conflicting results [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28]. This disparity may have been caused by small sample sizes, low statistical power, ethnic variability between studies, and/or clinical heterogeneity.…”