Previous studies in narcolepsy, an autoimmune disorder affecting hypocretin (orexin) neurons and recently associated with H1N1 influenza, have demonstrated significant associations with five loci. Using a well-characterized Chinese cohort, we refined known associations in TRA@ and P2RY11-DNMT1 and identified new associations in the TCR beta (TRB@; rs9648789 max P = 3.7×10⁻⁹ OR 0.77), ZNF365 (rs10995245 max P = 1.2×10⁻¹¹ OR 1.23), and IL10RB-IFNAR1 loci (rs2252931 max P = 2.2×10⁻⁹ OR 0.75). Variants in the Human Leukocyte Antigen (HLA)- DQ region were associated with age of onset (rs7744020 P = 7.9×10⁻⁹ beta −1.9 years) and varied significantly among cases with onset after the 2009 H1N1 influenza pandemic compared to previous years (rs9271117 P = 7.8×10⁻¹⁰ OR 0.57). These reflected an association of DQB1*03:01 with earlier onset and decreased DQB1*06:02 homozygosity following 2009. Our results illustrate how genetic association can change in the presence of new environmental challenges and suggest that the monitoring of genetic architecture over time may help reveal the appearance of novel triggers for autoimmune diseases. Narcolepsy-hypocretin deficiency results from a highly specific autoimmune attack on hypocretin cells. Recent studies have established antigen presentation by specific class II proteins encoded by (HLA DQB1*06:02 and DQA1*01:02) to the cognate T cell receptor as the main disease pathway, with a role for H1N1 influenza in the triggering process. Here, we have used a large and well-characterized cohort of Chinese narcolepsy cases to examine genetic architecture not observed in European samples. We confirmed previously implicated susceptibility genes (T cell receptor alpha, P2RY11), and identify new loci (ZNF365, IL10RB-IFNAR1), most notably, variants at the beta chain of the T cell receptor. We found that one HLA variant, (DQB1*03:01), is associated with dramatically earlier disease onset (nearly 2 years). We also identified differences in HLA haplotype frequencies among cases with onset following the 2009 H1N1 influenza pandemic as compared to before the outbreak, with fewer HLA DQB1*06:02 homozygotes. This may be the first demonstration of such an effect, and suggests that the study of changes in GWAS signals over time could help identify environmental factors in other autoimmune diseases.

Chronic intermittent hypoxia (CIH) is a serious consequence of obstructive sleep apnoea (OSA) and has deleterious effects on central neurons and neurocognitive functions. This study examined if protocatechuic acid (PCA) could improve learning and memory functions of rats exposed to CIH conditions and explore potential mechanisms. Neurocognitive functions were evaluated in male SD rats by step-through passive avoidance test and Morris water maze assay following exposure to CIH or room air conditions. Ultrastructure changes were investigated with transmission electron microscopy and neuron apoptosis was confirmed by TUNEL assays. Ultrastructure changes were investigated with transmission electron microscope and neuron apoptosis was confirmed by TUNEL assays. The effects of PCA on oxidative stress, apoptosis and brain IL-1β levels were investigated. Expression of Bcl-2, Bax, Cleaved Caspase-3, c-fos, SYN, BDNF and pro-BDNF were also studied along with JNK, P38 and ERK phosphorylation to elucidate the molecular mechanisms of PCA action. PCA was seen to enhance learning and memory ability and alleviate oxidative stress, apoptosis and glial proliferation following CIH exposure in rats. In addition, PCA administration also decreased the level of IL-1β in brain and increased the expression of BDNF and SYN. We conclude that PCA administration will ameliorate CIH-induced cognitive dysfunctions.

To evaluate the performance of a portable monitor (Nox-T3, Nox Medical Inc. Reykjavik, Iceland) used to diagnose obstructive sleep apnea in Chinese adults. Eighty Chinese adults (mean ± standard deviation age 47.6 ± 14.0 years, 77.5% males, body mass index 27.5 ± 5.4 kg/m²) underwent overnight, unattended home sleep apnea testing (HSAT) with the Nox-T3 portable monitor followed by an overnight in-laboratory polysomnogram (PSG) with simultaneous portable monitor recording. The portable monitor recordings were scored using automated analysis and then manually edited using different criteria for scoring hypopneas. Polysomnography was scored based on recommended guidelines. When scoring of hypopneas required a ≥ 4% oxygen desaturation event, the mean ± standard deviation apnea-hypopnea index (AHI) was 24.4 ± 20.8 events/h on HSAT, 28.0 ± 22.9 events/h on in-laboratory portable monitor recording, and 28.6 ± 23.9 events/h on PSG (P < .0001). Bland-Altman analysis of AHI on PSG versus HSAT showed a mean difference (95% confidence interval) of -4.64 (-7.15, -2.13); limits of agreement (equal to ± 2 standard deviations) was -26.62 to 17.35 events/h. Based on a threshold of AHI ≥ 5 events/h, HSAT had 95% sensitivity, 69% specificity, 94% positive predictive value, and 75% negative predictive value compared to PSG. Using an AHI ≥ 15 events/h, HSAT had 93% sensitivity, 85% specificity, 89% positive predictive value, and 91% negative predictive value. Closer agreements were present when comparing the simultaneous recordings. Similar results were obtained using different scoring criteria for hypopneas. Despite known differences between HSAT and PSG, the results show close agreement between the two diagnostic tests in Chinese adults, especially when controlling for night-to-night variability and changes in sleeping environment.