Ethnic differences in interleukin 6 (IL‐6) and IL6 receptor genes in spontaneous preterm birth and effects on amniotic fluid protein levels

Abstract

SummaryPreterm birth (PTB) is a significant neonatal health problem that is more common in African-Americans (AA) than in European-Americans (EA). Part of this disparity is likely to result from the differing genetic architectures of EA and AA. To begin assessing the role of these differences, patterns of genetic variation in two previously proposed candidate genes, encoding interleukin 6 (IL6) and its receptor (IL6R), were analyzed in mothers and fetuses from 496 EA birth-events (149 cases and 347 controls) and 397 birth-events in AA (76 cases and 321 controls). IL-6 levels in amniotic fluid (AF) samples were determined in a subset of these pregnancies. Case-control comparisons revealed a single SNP in IL6R associated with PTB (p=0.04 for allelic and p=0.05 for genotype association). In addition, all of the SNPs studied showed significant frequency differences between AA and EA in at least one comparison, significantly in excess of that expected from general population databases. Higher IL-6 concentrations were associated with the IL6 SNP -661 in EA preterm samples (p=0.0056), and this result seems to be driven by microbial invasion of the amniotic cavity, indicating a gene by infection interaction. These findings indicate that, as a function of IL6 genotype, EA and AA women respond differently to infection with respect to their expression of IL-6. Our data support differential genetic control of levels of IL-6 in amniotic fluid between EA and AA.

The effect of mentholated cigarette use on interleukin-6 responses across different HIV positive race/ethnic subgroups

“…In agreement with previous studies in the general population, our data have suggested racial differences on IL-6 levels. 4,5,28 Consistent with prior reports, differences in IL-6 production were evident between non-Hispanic Caucasians, Hispanics, and African Americans, with African Americans exhibiting the lowest IL-6 levels. 29 More critically, however, our study extends earlier findings by showing, for the first time, that using mentholated cigarettes may impose additional burdens on the body's regulation of inflammatory response among African Americans and Hispanics living with HIV.…”

Novel biomarkers for the prediction of the spontaneous preterm birth phenotype: a systematic review and meta-analysis

“…99,100 In fact, the concentrations of interleukins-6 and -8 in the amniotic fluid were similar between preterm and term samples in African Americans, whereas they were significantly higher in European American cases compared with European American controls. 99,101 If these findings are confirmed, it would indicate that predictive biomarkers in this condition perform differently across ethnic populations and/or geographical locations. Fourth, novel biomarkers could have different predictive ability depending upon the gestational age at birth.…”

Combined effect of C-reactive protein gene SNP +2147 A/G and interleukin-6 receptor gene SNP rs2229238 C/T on anthropometric characteristics among school children in Taiwan

“…[34][35][36] Gender differences in IL-6 production have been reported in previous studies; 37,38 therefore, IL-6 or IL-6R polymorphisms that modify IL-6 levels might potentially contribute to sex disparity. For the IL-6R polymorphisms, some studies have focused on women (studying IL-6 levels, CRP levels, bone mineral density, obesity, hyperandrogenism, preterm birth, type 2 diabetes and melanoma), 7,29,[39][40][41][42][43][44] and one on men (studying obesity). 45 Most analyses of IL-6R gene polymorphisms have not investigated (or at least have not reported) gender differences.…”