IL10 Haplotype Associated with Tuberculin Skin Test Response but Not with Pulmonary TB

Evidence from genetic association and twin studies indicates that susceptibility to tuberculosis (TB) is under genetic control. One gene implicated in susceptibility to TB is that encoding interleukin-10 (IL10). In a group of 2010 Ghanaian patients with pulmonary TB and 2346 healthy controls exposed to Mycobacterium tuberculosis, among them 129 individuals lacking a tuberculin skin test (PPD) response, we genotyped four IL10 promoter variants at positions −2849 , −1082 , −819 , and −592 and reconstructed the haplotypes. The IL10 low-producer haplotype −2849A/−1082A/−819C/−592C, compared to the high-producer haplotype −2849G/−1082G/−819C/−592C, occurred less frequent among PPD-negative controls than among cases (OR 2.15, CI 1.3–3.6) and PPD-positive controls (OR 2.09, CI 1.2–3.5). Lower IL-10 plasma levels in homozygous −2849A/−1082A/−819C/−592C carriers, compared to homozygous −2849G/−1082G/−819C/−592C carriers, were confirmed by a IL-10 ELISA (p = 0.016). Although we did not observe differences between the TB patients and all controls, our results provide evidence that a group of individuals exposed to M. tuberculosis transmission is genetically distinct from healthy PPD positives and TB cases. In these PPD-negative individuals, higher IL-10 production appears to reflect IL-10-dependent suppression of adaptive immune responses and sustained long-term specific anergy

Genetic polymorphism of the methotrexate transporter ABCG2, blood pressure and markers of arterial function in patients with rheumatoid arthritis: repeated cross-sectional study

Leena R Baghdadi,1 Richard J Woodman,2 E Michael Shanahan,3 Michael D Wiese,4 Arduino A Mangoni5 1Department of Family and Community Medicine, College of Medicine, King Saud University and King Khalid University Hospital, Riyadh, Saudi Arabia; 2Centre for Epidemiology and Biostatistics, College of Medicine and Public Health, Flinders University, Adelaide, SA, Australia; 3Department of Rheumatology, College of Medicine and Public Health, Flinders University and Southern Adelaide Local Health Network, Adelaide, SA, Australia; 4School of Pharmacy and Medical Sciences and Sansom Institute for Health Research, University of South Australia, Adelaide, SA, Australia; 5Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University and Flinders Medical Centre, Adelaide, SA, Australia Purpose: Methotrexate (MTX) treatment is associated with lower blood pressure (BP) and arterial stiffness in rheumatoid arthritis (RA). We investigated associations between single-nucleotide polymorphism (SNP) of the ATP-binding cassette efflux transporter gene ABCG2 (rs2231142), BP, and arterial stiffness in RA patients treated with MTX. Patients and methods: Clinical and 24-hour peripheral and central BP, arterial wave reflection (Augmentation Index, AIx), arterial stiffness (Pulse Wave Velocity, PWV), and intracellular MTX polyglutamate (MTXPGs) concentrations were assessed in 56 RA patients on stable treatment with MTX using a repeated cross-sectional study design with measurements at baseline and after 8 months. Results: Majority of the RA patients were homozygotes for the normal allele (CC, n=46) whereas 10 were rs2231142 heterozygotes (AC, n=10). MTXPGs concentrations were non-significantly higher in AC when compared to CC (144.3 vs 116.3 nmol/L packed RBCs, P=0.10). At baseline, the AC group had significantly lower age-adjusted clinical systolic BP (SBP) (P=0.01), 24-hour peripheral SBP (P=0.003), and central SBP (P=0.02) when compared to the CC group. However, AIx and PWV values were not significantly different between the two groups. When data from both visits were combined in a single analysis, and additionally adjusted for visit, gender, body mass index, and Disease Activity Score 28, the trend in SBP differences between-groups persisted but was no longer significant. Conclusion: Future studies are required to test the hypothesis that this genetic polymorphism is associated with lower BP, arterial stiffness, and possibly, cardiovascular risk, in RA patients treated with MTX. Keywords: methotrexate, disease-modifying antirheumatic drugs, blood pressure, augmentation index, rheumatoid arthritis, pulse wave velocity, single-nucleotide polymorphisms, ATP-binding cassette transporters, ABCG

HPV at the time of vaccine: has screening reached its goal?

Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on reproductive outcomes after ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. This systematic review and meta-analysis assessed the strength of the association between obesity and ovulation or pregnancy rates after OAT. MEDLINE and several other databases were searched from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the relative risk of reproductive outcomes (ovulation and pregnancy) in lean (body mass index <25 kg/m(2)) compared with overweight or obese women. The study obtained 15 data sets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) compared with obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. It is concluded that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively. Obesity is known to interfere with reproductive outcomes in polycystic ovary syndrome. There is no consensus regarding the impact of obesity on ovarian ablative therapy (OAT) and there is no level I evidence to answer this question. We therefore undertook a systematic review and meta-analysis to assess the strength of the association between obesity and ovulation or pregnancy rates after OAT. We searched MEDLINE and several other databases from 2000 to September 2011 for studies reporting on OAT and reproductive outcomes. Data were synthesized to determine the risk ratio of reproductive outcomes (ovulation and pregnancy) in lean (BMI <25 kg/m(2)) as opposed to overweight or obese women. We obtained 15 datasets (14 articles) for analysis, which included 905 subjects in the obese group and 879 subjects in the lean group. Lean women had increased ovulation rates (RR 1.43, 95% CI 1.22-1.66) as compared to obese women. Pregnancy rates also showed a similar trend (RR 1.73, 95% CI 1.39-2.17). Reproductive outcomes were generally better in younger women, more recent studies and randomized controlled trials. We conclude that lean women respond better to OAT than their obese counterparts. These epidemiological observations indicate that obesity alters reproductive outcomes after OAT negatively