DESIGN: Meta-analysis of odds ratios.
SETTING: Not applicable.
PATIENT(S): Subjects were women with RPL and their partners.
INTERVENTION(S): Not applicable.
MAIN OUTCOME MEASURE(S): The association between M2/ANXA5 haplotype and RPL was evaluated in a meta-analysis of odds ratios. We further scrutinized this association according to [1] the sequence of miscarriages, [2] the number of consecutive losses, [3] the extent of excluding other pathologies of RPL, and [4] the timing of fetal loss.
RESULT(S): Fourteen individual studies (n = 4,664 subjects) were included in this meta-analysis. The results show that women with the M2/ANXA5 haplotype have 1.54 times (95% confidence interval, 1.08-2.20) the odds of having associated RPL compared with women with the normal haplotype, regardless of consecutive or nonconsecutive pregnancy losses. Acknowledging the clinical heterogeneity among the studies, this significant association comes with a caveat that the lower bound of the confidence interval is close to unity. In couple populations (n = 2,449), M2/ANXA5 haplotype subjects have an odds ratio of 1.48 (95% confidence interval, 1.14-1.91) of experiencing RPL, which suggests contributions from paternal M2/ANXA5 carriers in RPL.
CONCLUSION(S): This meta-analysis ascertains that women with the M2/ANXA5 haplotype have a higher risk of experiencing RPL, especially consecutive early idiopathic RPL. Male partners with the M2/ANXA5 haplotype partly contribute to this risk. Hence, screening for the M2/ANXA5 haplotype as a panel of laboratory investigations for RPL is recommended.
METHODS: A systematic review was performed for all the articles retrieved from multiple databases, up until March 2017. Data were extracted from all eligible studies, and meta-analysis was carried out using RevMan 5.3 and R package 3.2.1. The strength of association between each studied polymorphism and ischemic stroke risk was measured as odds ratios (ORs) and 95% confidence intervals (CIs), under fixed- and random-effect models.
RESULTS: A total of 79 studies reporting on the association between the studied polymorphisms and ischemic stroke risk were identified. The pooled data indicated that all genetic models of APOA5 rs662799 (ORs = 1.23-1.43), allelic and over-dominant models of APOA5 rs3135506 (ORs = 1.77-1.97), APOB rs1801701 (ORs = 1.72-2.13) and APOB rs1042031 (ORs = 1.66-1.88) as well as dominant model of ABCA1 rs2230806 (OR = 1.31) were significantly associated with higher risk of ischemic stroke. However, no significant associations were observed between ischemic stroke and the other five polymorphisms, namely ApoB (rs693) and APOC3 (rs4520, rs5128, rs2854116 and rs2854117), under any genetic model.
CONCLUSIONS: The present meta-analysis confirmed a significant association of APOA5 rs662799 CC, APOA5 rs3135506 CG, APOB rs1801701 GA, APOB rs1042031 GA and ABCA1 rs2230806 GG with increased risk of ischemic stroke.
METHODS: Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to genotype all the aforementioned gene polymorphisms. Kaplan-Meier survival function, log-rank test and Cox regression were used to investigate the effect of gene polymorphisms on the all-cause survival of NPC.
RESULTS: NPC cases carrying T/T genotype of ITGA2 C807T have poorer all-cause survival compared to those with C/C genotypes, with an adjusted HR of 2.06 (95% CI = 1.14-3.72) in individual model. The 5-year survival rate of C/C carriers was 55% compared to those with C/T and T/T where the survival rates were 50% and 43%, respectively.
CONCLUSION: The finding from the present study showed that ITGA2 C807T polymorphism could be potentially useful as a prognostic biomarker for NPC. However, the prognostic value of ITGA2 C807T polymorphism has to be validated by well-designed further studies with larger patient numbers.
METHODS: We conducted a 1 to N case-control study involving 300 nasopharyngeal carcinoma (NPC) cases and 533 controls matched by age, gender and ethnicity to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and XPD Lys751Gln polymorphisms on NPC risk. Linkage disequilibrium and haplotype analysis were conducted to explore the association of allele combinations with NPC risk. Restriction fragment length polymorphism (RFLP-PCR) was used for DNA genotyping.
RESULTS: No significant association was observed between hOGG1 Ser326Cys and ITGA2 C807T polymorphisms with NPC risk after adjustment for age, gender, ethnicity, cigarette smoking, alcohol and salted fish consumption. Lys/Lys genotype of XPD Lys751Gln polymorphism was associated with increased NPC risk (OR = 1.60, 95% CI = 1.06-2.43). Subjects with history of smoking (OR = 1.81, 95% CI = 1.26-2.60), and salted fish consumption before age of 10 (OR = 1.77, 95% CI = 1.30-2.42) were observed to have increased odds of NPC. The odds of developing NPC of CGC haplotype was significantly higher compared to reference AGC haplotype (OR = 2.20, 95% CI = 1.06-4.58).
CONCLUSION: The allele combination of CGC from hOGG1, ITGA2 and XPD polymorphisms was significantly associated with increased odds of NPC.
METHODS: We used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes.
RESULTS: Compared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [- 0.8; 0.9], respectively).
CONCLUSIONS: The consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.