Kawasaki disease is a systemic vasculitis of unknown etiology, with clinical observations suggesting a substantial genetic contribution to disease susceptibility. We conducted a genome-wide association study and replication analysis in 2,173 individuals with Kawasaki disease and 9,383 controls from five independent sample collections. Two loci exceeded the formal threshold for genome-wide significance. The first locus is a functional polymorphism in the IgG receptor gene FCGR2A (encoding an H131R substitution) (rs1801274; P = 7.35 × 10(-11), odds ratio (OR) = 1.32), with the A allele (coding for histadine) conferring elevated disease risk. The second locus is at 19q13, (P = 2.51 × 10(-9), OR = 1.42 for the rs2233152 SNP near MIA and RAB4B; P = 1.68 × 10(-12), OR = 1.52 for rs28493229 in ITPKC), which confirms previous findings(1). The involvement of the FCGR2A locus may have implications for understanding immune activation in Kawasaki disease pathogenesis and the mechanism of response to intravenous immunoglobulin, the only proven therapy for this disease.

Children born small for gestational age (SGA) have several life-long consequences. Previous epidemiological studies investigated from childhood to adulthood reported that a number of chronic diseases originate in the prenatal period. With the emerging era of obesity epidemic, more concerns are related to being obese than being short-statured in SGA children. The exact mechanisms are uncertain; however, growth hormone-insulin-like growth factor axis disturbance by fetal programming and accelerated postnatal weight gain contributed to central adiposity in SGA children. In this review, we summarized the definitions and prevalence of SGA, epidemiology, and general risks of obesity in SGA children. Early interventions, before and after birth, are needed for healthy catch-up growth to prevent later obesity and related complications.

PurposeGonadotropin-releasing hormone agonist (GnRHa) is known for improving final adult height in patients with central precocious puberty (CPP). This study aimed to investigate the age of menarche and near adult height in girls with CPP who had been treated with GnRHa.MethodsIn this retrospective study, we reviewed the medical records of 71 Korean girls with CPP who had started menarche or reached over 13 years of bone age after long-term GnRHa treatment. We estimated near adult height using the Bayley-Pinneau method and identified the age of menarche in girls with CPP.ResultsMean chronological and bone age at menarche were 11.9±0.7 and 12.8±0.4 years, respectively. The period between menarche and the end of treatment was 14.0±5.6 months. Posttreatment near adult height was 163.8±4.7 cm, which was significantly greater than pretreatment predicted adult height (158.7±4.1 cm).ConclusionGnRHa treatment in girls with CPP could improve final adult height and made the age of menarche close to that of the general population.

T and b TaqI and BsmI alleles are protective against T1DM in Korean subjects.

Sometimes, the clinical findings and the results of the gonadotropin-releasing hormone (GnRH) stimulation test are inconsistent in girls with early breast development and bone age advancement. We aimed to investigate the factors predicting positive results of the GnRH stimulation test in girls with suspected central precocious puberty (CPP). We reviewed the records of 574 girls who developed breast budding before the age of 8 yr and underwent the GnRH stimulation test under the age of 9 yr. Positive results of the GnRH stimulated peak luteinizing hormone (LH) level were defined as 5 IU/L and over. Girls with the initial positive results (n = 375) showed accelerated growth, advanced bone age and higher serum basal LH, follicle-stimulating hormone, and estradiol levels, compared to those with the initial negative results (n = 199). Girls with the follow-up positive results (n = 64) showed accelerated growth and advanced bone age, compared to those with the follow-up negative results. In the binary logistic regression, the growth velocity ratio was the most significant predictive factor of positive results. We suggest that the rapid growth velocity is the most useful predictive factor for positive results in the GnRH stimulation test in girls with suspected precocious puberty.

Kawasaki disease (KD) is often complicated by coronary artery lesions (CALs), including aneurysms. Because of the complications associated with KD, this disorder is the leading cause of acquired heart disease in children from developed countries. To identify genetic loci that confer a higher risk of developing CALs, we performed a case-control association study using previous genome-wide association study data for samples from KD cases only (n=186) by grouping KD patients without CALs (control: n=123) vs KD patients with extremely large aneurysms (diameter>5 mm) (case: n=17). Twelve loci with one or more sequence variants were found to be significantly associated with CALs (P<1 × 10(-5)). Of these, an SNP (rs17136627) in the potassium intermediate/small conductance calcium-activated channel, subfamily N, member 2 (KCNN2) at 5q22.3 was validated in 32 KD patients with large aneurysms (diameter>5 mm) and 191 KD patients without CALs (odds ratio (OR)=12.6, P(combined)=1.96 × 10(-8)). This result indicates that the KCNN2 gene can have an important role in the development of coronary artery aneurysms in KD.

Although the prevalence of childhood obesity in Korea was similar since early 2000s, extreme obesity prevalence has increased, especially among teenage boys. Considering greater morbidity risks, preventing progression to extreme obesity is crucial.

PurposeLow vitamin D level is common in adults with diabetes mellitus (DM). We assessed vitamin D level and its associated factors in Korean youth with type 1 DM. MethodsType 1 DM cases (n=85) and healthy controls (n=518) aged <20 years were included and grouped into 3 categories according to vitamin D level: deficiency (<20 ng/mL), insufficiency (20–30 ng/mL), or sufficiency (≥30 ng/mL).ResultsThe mean serum vitamin D level was significantly lower (21.6±8.5 ng/mL vs. 28.0±12.0 ng/mL, P<0.001) and vitamin D deficiency prevalence was significantly higher (48% vs. 26%, P<0.001) in type 1 DM cases than in healthy controls. Logistic regression analysis revealed that type 1 DM cases were more likely to have vitamin D deficiency (P=0.004), independent of sex, age, and body mass index. Type 1 DM cases with vitamin D deficiency/insufficiency were mainly diagnosed in winter (November to April) (P=0.005), and the duration of diabetes was longer than in those with vitamin D sufficiency (P=0.046). However, season of diagnosis, duration of diabetes, prescribed daily insulin dose, and glycosylated hemoglobin and C-peptide levels were not associated with 25-hydroxyvitamin D (25(OH)D) level in type 1 DM cases after adjustment for other factors.ConclusionsWe recommend assessment of serum 25(OH)D level in type 1 DM cases and to treatment if findings indicate insufficiency. Further studies investigating the mechanisms underlying vitamin D deficiency in youth with type 1 DM are needed.