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The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

In patients with hyperlipidemia, the risk of retear increases after rotator cuff repair (RCR). In particular, it has been reported that preoperative low-density lipoprotein cholesterol (LDL-C) level affects cuff integrity. However, there are no studies assessing whether lipidemic control affects cuff healing.To evaluate the effect of preoperative lipidemic control on cuff integrity after arthroscopic RCR across cardiovascular disease risk groups in patients with hyperlipidemia.Case-control study; Level of evidence, 3.The authors retrospectively reviewed the charts of patients with hyperlipidemia who underwent arthroscopic double-row suture bridge RCR between 2014 and 2019. The included patients had LDL-C tested within 1 month before surgery. Magnetic resonance imaging was conducted 6 months after surgery to evaluate the integrity of the repaired cuff tendon. Patients were divided into groups of low, moderate, high, and very high risk according to the 4th Korean Dyslipidemia Guidelines. On the basis of the target LDL-C set in each risk group, patients were categorized into 2 groups: group C (controlled hyperlipidemia, less than target LDL-C) and group U (uncontrolled hyperlipidemia, target LDL-C or greater). The correlation between serum lipid profile, lipidemic control, and post-RCR integrity was evaluated.A total of 148 patients were analyzed, 51 in group U and 97 in group C. The retear rate was significantly higher in group U than in group C (23/51 [45.1%] vs 18/97 [18.6%], respectively; P = .001). The proportion of group U was significantly higher in the retear group than in the healing group (56.1% vs 26.2%; P = .001). In addition, the proportions of patients with uncontrolled diabetes mellitus (DM) (19.5% vs 3.7%; P = .002) and mediolateral (2.6 ± 1.2 cm vs 1.7 ± 1.1 cm; P < .001) and anteroposterior (2.2 ± 1.1 cm vs 1.6 ± 0.8 cm; P = .003) tear sizes were significantly different between the retear and healing groups, respectively. No significant difference in serum lipid profile, including LDL-C level (119.6 ± 31.3 vs 116.7 ± 37.2; P = .650), was observed between the retear and healing groups. Multivariate regression analysis identified uncontrolled hyperlipidemia (OR, 4.005; P = .001), uncontrolled DM (OR, 5.096; P = .022), and mediolateral tear size (OR, 1.764; P = .002) as independent risk factors for retear. The 2.0-cm mediolateral size cutoff and the 3 independent risk factors had significant associations with retear.Poor preoperative lipidemic control was significantly associated with poor healing after RCR. In addition to large mediolateral tear size, uncontrolled hyperlipidemia and DM were significant risk factors for retear. Moreover, poor lipidemic control compared with the recommended target level before surgery was more correlated with an increased retear rate than a preoperative LDL-C level. [ABSTRACT FROM AUTHOR]

Kawasaki disease (KD) is an acute systemic vasculitis that can potentially cause coronary artery aneurysms in some children. KD occurs approximately 1.5 times more frequently in males than in females. To identify sex-specific genetic variants that are involved in KD pathogenesis in children, we performed a sex-stratified genome-wide association study (GWAS), using the Illumina HumanOmni1-Quad BeadChip data (249 cases and 1,000 controls) and a replication study for the 34 sex-specific candidate SNPs in an independent sample set (671 cases and 3,553 controls). Male-specific associations were detected in three common variants: rs1801274 in FCGR2A [odds ratio (OR) = 1.40, P = 9.31 × 10−5], rs12516652 in SEMA6A (OR = 1.87, P = 3.12 × 10−4), and rs5771303 near IL17REL (OR = 1.57, P = 2.53 × 10−5). The male-specific association of FCGR2A, but not SEMA6A and IL17REL, was also replicated in a Japanese population (OR = 1.74, P = 1.04 × 10−4 in males vs. OR = 1.22, P = 0.191 in females). In a meta-analysis with 1,461 cases and 5,302 controls, a very strong association of KD with the nonsynonymous SNP rs1801274 (p.His167Arg, previously assigned as p.His131Arg) in FCGR2A was confirmed in males (OR = 1.48, P = 1.43 × 10−7), but not in the females (OR = 1.17, P = 0.055). The present study demonstrates that p.His167Arg, a KD-associated FCGR2A variant, acts as a susceptibility gene in males only. Overall, the gender differences associated with FCGR2A in KD provide a new insight into KD susceptibility. [ABSTRACT FROM AUTHOR]