Polymorphims in the Interferon-y/Interleukin 26 Gene Region Contribute to Sex Bias in Susceptibility to Rheumatoid Arthritis

Objective:

To determine whether polymorphisms in the interferon-? (IFN?)/interleukin-26 (IL-26; formerly, AK155) gene cluster contribute to sex-based differential susceptibility to rheumatoid arthritis (RA).

Methods:

Four microsatellite markers, located in a 118-kb interval that contains both the IFN? and IL-26 genes on chromosome 12q15, were typed in 251 patients with RA and 198 unrelated healthy controls (all of whom lived in Northern Ireland) by means of polymerase chain reaction–based fragment analysis.

Results:

Marker D12S2510, which is located 3 kb 3' from the IL-26 gene, was significantly associated with RA in women (corrected P [Pcorr] = 0.008, 2 degrees of freedom [2 df]) but not in men (P = 0.99, 2 df). A 3-marker haplotype, IFNGCA*13;D12S2510*8;D12S2511*9, was inferred that showed significant underrepresentation in women with RA (odds ratio 0.50, 95% confidence interval 0.32–0.78; P = 0.002, Pcorr = 0.03) but not in men with RA.

Conclusion:

Our results demonstrate that common polymorphisms in the IFN?/IL-26 gene region may contribute to sex bias in susceptibility to RA, by distorting the propensity of female carriers versus male carriers to contract this disease. These results conform to our recent observations of a role for this gene cluster in sex-based differential susceptibility to another Th1-type inflammatory disease, multiple sclerosis.

Interleukin 3 and schizophrenia:the impact of sex and family history

Chromosome 5q21-33 has been implicated in harboring risk genes for schizophrenia. In this paper, we report evidence that multiple single nucleotide polymorphisms in and around interleukin 3 (IL3) are associated with the disease in the Irish Study of High-Density Schizophrenia Families (ISHDSF), the Irish Case-Control Study of Schizophrenia (ICCSS) and the Irish Trio Study of Schizophrenia (ITRIO). The associations are sex-specific and depend on the family history (FH) of schizophrenia. In all three samples, rs31400 shows female-specific and FH-dependent associations (P=0.0062, 0.0647 and 0.0284 for the ISHDSF, ICCSS and ITRIO, respectively). Several markers have similar associations in one or two of the three samples. In haplotype analyses, identical risk and protective haplotypes are identified in the ISHDSF and ITRIO samples in several multimarker combinations. For ICCSS, the same haplotypes are implicated; however, the risk haplotypes observed in the family samples become protective. Several significant markers, rs440970, rs31400 and rs2069803, are located in and around known estrogen response elements, promoter and enhancer of the IL3 gene. They may explain the sex-specific associations and be functional for the expression of IL3 gene.

Chromosome 2q31. 1 associates with ESRD in women with type 1 diabetes

Sex and genetic variation influence the risk of developing diabetic nephropathy and ESRD in patients with type 1 diabetes. We performed a genome-wide association study in a cohort of 3652 patients from the Finnish Diabetic Nephropathy (FinnDiane) Study with type 1 diabetes to determine whether sex-specific genetic risk factors for ESRD exist. A common variant, rs4972593 on chromosome 2q31. 1, was associated with ESRD in women (P

A rapid dot-blot assay to assess chimerism following sex-mismatched bone marrow transplantation

Mixed chimerism may occur more frequently than previously thought following allogeneic bone marrow transplantation and may have implications in terms of relapse, graft-versus-host disease and immune reconstitution. DNA analysis using single or multilocus polymorphic probes cannot reliably discriminate between donor and recipient cells below a level of 10%. We used probe pHY2.1, a cloned segment of tandemly repeated DNA (2000 copies) on the long arm of chromosome Y. A dot blot procedure allowed us to immobilize DNA directly from 50 microliter of peripheral blood or bone marrow. Cross-reactivity was eliminated by hybridization at conditions of extreme stringency (65 degrees C, 50% formamide). Mixing experiments detected male DNA at a level of 0.1% after 10 h exposure. Five patients were studied serially post-bone marrow transplantation. One patient showed mixed chimerism for 12 months, one had complete autologous recovery and the remaining three showed complete engraftment. All results were verified by standard karyotyping on bone marrow cells. This technique is a simple, rapid and sensitive assay for chimerism following sex mismatched bone marrow transplantation.

Sex Education in Northern Ireland Schools: a Critical Evaluation.

To date there has been little research on young people and sexuality in Northern Ireland. This paper draws on the first major study in this area to analyse the delivery of formal sex education in schools. Both quantitative and qualitative methods were used to access young people's opinions about the quality of the sex education they had received at school. Overall, they reported high levels of dissatisfaction, with notable variations in relation to both gender and religious affiliation. In one sense their opinions mesh well with those of young people in other parts of these islands. At the same time the specificity of sexuality in Ireland plays a key role in producing the moral system that underlies much of formal sex education in schools. Underpinned by a particularly traditional and conservative strain of Christian morality, sex education in Northern Ireland schools is marked by conservatism and silence and by the avoidance of opportunities for informed choice in relation to sexuality on the part of young people.

The first time: young people and sex in Northern Ireland.

The sexual health of people, particularly young people, in Northern Ireland is currently poor. Yet there has been little research conducted on sexual attitudes and lifestyles. This paper is based on data from the first ever major research project in this field in Northern Ireland. Using quantitative and qualitative methods, it targeted young people aged 14-25. A combination of a self-administered survey questionnaire, focus group discussions and one-to-one interviews was found to be most suitable for the collection of sensitive data on sexuality in a country where the social and moral climate had previously prevented studies of this nature. Information was collected on sexual attitudes and behaviour generally. This paper focuses on one crucial issue: the age of first sexual encounter. It explores the attitudes of young people to that experience and the use of contraception. Many of the findings match those of similar large-scale surveys in England and Wales, including the modal age of first sexual encounter and the influence of peer pressure on decision-making about first sex. There were significant gender differences in both behaviour and attitudes. It is hoped that the research results will influence future education and health policy, which has all too often been based on ignorance.

Diagnosing child sex abuse: A research challenge.

Child sex abuse increasingly is recognised as a societal problem that can no longer be ignored. In this paper definitions, prevalence, trends, assessment, and available diagnostic procedures are described and critically evaluated. It is argued that the lack of reliable diagnostic procedures remains one of the main difficulties in dealing effectively with the detrimental effects of CSA on the child or adult. The research challenge to find effective alternative procedures is outlined.