Genome-wide association (GWA) studies revealed a number of single nucleotide polymorphisms (SNPs) significantly associated with type 1 diabetes (T1D). In an attempt to confirm some of these candidate associations, we genotyped 2046 Caucasian patients and 2417 normal controls from the United States for SNPs in five genomic regions. While no evidence was obtained for four genomic regions (rs2929366/NM_144715 on chromosome 3, rs9127/Q7Z4C4 on chromosome 5, rs1445898/CAPSL on chromosome 5 and rs2302188/NM_033543 on chromosome 19), we provide strong evidence for association between T1D and multiple SNPs in the IFIH1 linkage disequilibrium (LD) block on chromosome 2q. Among the 10 SNPs genotyped for the 2q region, four SNPs located within the IFIH1 gene or at the 5' region of IFIH1 showed significant association with T1D in the Georgia population [odds ratio (OR) = 1.7-1.9] with the best P-value found at SNP rs1990760 (P = 8 x 10(-8) and OR = 1.9). Several SNPs outside of the IFIH1 gene also showed significant but weaker associations. Furthermore, IFIH1 gene expression levels in peripheral blood mononuclear cells are significantly correlated with IFIH1 genotypes, and higher IFIH1 levels are found in individuals with the susceptible genotypes (P = 0.005). Thus, both genetic association and gene expression data suggest that IFIH1 is the most plausible candidate gene implicated in T1D in this LD block.

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BACKGROUND: Risk factors for cardiovascular disease, the leading cause of death, have been documented in children as young as 3 years of age. Maternal environment (eg, exercise) influences fetal development and long-term health. Thus, the development of the fetal cardiovascular system during pregnancy is likely a preliminary indicator of cardiac health at birth and a proxy for the future risk of cardiovascular disease throughout life. OBJECTIVE: The purpose of this study was to assess the effects of supervised prenatal aerobic exercise at recommended levels on fetal cardiac function and outflow in the third trimester of pregnancy. We hypothesized that fetuses of aerobically trained women compared with fetuses of nonexercising women would exhibit increased cardiac function and greater cardiac output. STUDY DESIGN: Secondary data analyses of a 20-week, randomized controlled exercise intervention trial in pregnant women between 2015 and 2018 in Eastern North Carolina were performed. Eligibility criteria included pregnant women <16 weeks gestation, singleton pregnancy, aged 18e40 years, body mass index of 18.5e34.99 kg/m 2 , physician clearance letter for exercise participation, reliable transportation, and method of communication. Exclusion criteria included the presence of chronic conditions (eg, type 1 or 2 diabetes mellitus), current medications known to adversely affect fetal growth (eg, antidepressants), alcohol, smoking, or illicit drug use. The patient cohort consisted of 133 eligible pregnant women who were assigned randomly to either an aerobic exercise (n¼66) group that participated in 150 minutes of supervised, moderate-intensity (40-59% VO 2peak ; 12e14 on Borg Rating of Perceived Exertion) aerobic exercise per week or a nonexercising group (n¼61) that consisted of 150 minutes per week of light (<40% VO 2peak ) stretching and relaxation breathing techniques. Between 34 and 36 weeks gestation, a fetal echocardiogram was performed to assess fetal cardiac function, which included fetal heart rate, right-and left-ventricular stroke volume, stroke volume index, cardiac output, cardiac output index, and cardiac outflow that included pulmonary and aortic valve diameters, peak flow velocity, and peak flow velocity-time integral. Fetal activity state (quiet vs active) during the echocardiogram and maternal aerobic capacity served as covariates. Intention-to-treat and per-protocol (participants who attended !80% of exercise sessions) analysis of covariance regression models were performed. RESULTS: Of the 127 randomly assigned participants, 66 and 50 participants were included in the intention-to-treat and per-protocol analyses, respectively. Prenatal aerobic exercise significantly increased fetal right-ventricular cardiac measures of right ventricular stroke volume (P¼.001) and stroke index via velocity-time integral (P¼.003), right ventricular cardiac output (P¼.002), cardiac index via velocity-time integral (P¼.006), pulmonary artery diameter (P¼.02), and pulmonary valve velocity-time integral (P¼.03). Only in ...

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Purpose: The objective of this study is to assess the effects of supervised, recommended levels of prenatal aerobic exercise on 1-month-old infant cardiac function. Methods: Eligible pregnant women were randomly assigned to either an aerobic exercise group that participated in 150 min of supervised, moderate-intensity (40% to 59% VO 2peak , 12 to 14 on Borg rating of perceived exertion) aerobic exercise per week for 24 wk or more or a nonexercising group that consisted of 150 min•wk −1 of relaxation techniques. One-month-old infant echocardiogram was performed to assess infant cardiac function, including heart rate (HR), left-ventricular stroke volume, cardiac output, cardiac index, ejection fraction, fractional shortening, and velocity time integral at the aortic valve. Pearson correlation analyses and linear regression models were performed. Results: Prenatal aerobic exercise was negatively correlated with infant resting HR (r = −0.311, P = 0.02). Similarly, when controlling for infant sex and activity state, exercise level/volume (β = −0.316; 95% CI, −0.029 to −0.002; P = 0.02) predicted resting infant HR (R 2 = 0.18, P = 0.02). In infants of overweight/obese women, infants of aerobic exercisers had increased fractional shortening (P = 0.03). In addition, infant ventricular ejection fraction was correlated with maternal exercise attendance (r = 0.418, P = 0.03) as well as a trend for exercise level (r = 0.351, P = 0.08). Similarly, the only significant regression model for infants of overweight/obese women controls infant activity state ( β = −0.444; 95% CI, −0.05 to −0.01; P = 0.006) and maternal exercise level (β = 0.492; 95% CI, 5.46-28.74; P = 0.01) predicting infant resting HR (F = 5.79, R 2 = 0.40, P = 0.003). Conclusions: The findings of this study demonstrate that women participating in exercise in the second and third trimesters of their pregnancy may have infants with increased cardiac function at 1 month of age. Importantly, the cardiac function effects were further augmented for infants born to overweight/obese women.