Nak Hoon Son

Associations between genetic variants in the IRGM gene and inflammatory bowel diseases in the korean population

Background:Recent European ancestry genome-wide association studies have identified genetic variants of IRGM as significant susceptibility loci for Crohns disease (CD). Therefore, we investigated whether genetic variants of IRGM confer genetic susceptibility to CD or ulcerative colitis (UC) and evaluated the genotype–phenotype associations in the Korean population. Methods:This study included 510 inflammatory bowel disease (IBD) patients (253 patients with CD and 257 with UC) and 520 healthy controls in Koreans. Initially, we performed direct sequencing analysis to identify unique IRGM single nucleotide polymorphisms (SNPs). Three selected haplotype-tagging SNPs and one risk locus (rs72553867, rs10065172, rs4958847, and rs12654043) within the IRGM were then geno-typed in patients and controls. Results:IRGM SNP rs10065172 was significantly associated with CD susceptibility in terms of allelic frequency (P = 0.004; odds ratio [OR] = 1.42) and genotype frequency (dominant model, P = 0.008; OR = 1.62). We also found a relationship between SNP rs72553867 and CD susceptibility in the analysis of allelic frequency (P = 0.0117; OR = 0.67) and genotype frequency (dominant model, P = 0.002; OR = 0.55). In addition, we observed that the association of CD with rs10065172 became stronger in patients with younger age at diagnosis (⩽20 years) or male gender. However, there was no significant association between the four SNPs and UC susceptibility. Conclusions:This is the first study to identify SNP rs10065172 and rs72553867 in IRGM as principal CD susceptibility loci in an Asian population.

Adiponectin and progression of arterial stiffness in hypertensive patients

BACKGROUND Recent studies suggest that adiposity is associated with arterial stiffness. However, it is unclear which adipokine or what adiposity related parameters are related with the progression of arterial stiffness. We hypothesized that in hypertensive patients, initial levels of adipokines such as adiponectin and resistin are related to the progression of arterial stiffness, which has been proven to be associated with increased risk of cardiovascular events. METHODS One hundred forty one consecutive patients with treated essential hypertension (81 men, 57.7±8.2 years) were enrolled. Pulse wave velocity (PWV) was measured at baseline, and after 24 months. Clinical variables and laboratory findings at the time of initial enrollment were analyzed to reveal the determinants of arterial stiffening. RESULTS Mean heart to femoral PWV (hfPWV) was 992±202 cm/s at baseline, and 1021±263 cm/s at 24 months follow up. hfPWV progressed in seventy two patients (51.1%) during follow up period. In patients with hfPWV progression, mean plasma adiponectin level was significantly lower than patients with nonprogression (progressor: 5.18±3.21 μg/ml, non-progressor: 7.02±5.19 μg/ml, p=0.013). Multivariate regression analysis revealed plasma adiponectin level to being an independent predictor of hfPWV changes (ß=-0.018, p=0.032) when controlled for age, gender, SBP changes, BP control and HOMA. CONCLUSIONS Plasma adiponectin levels are associated with progression of arterial stiffness in hypertensive patients. These findings may be one explanation for the high association between adiposity and arterial stiffness in hypertensive patients.

Trends in renal function after radical nephrectomy: a multicentre analysis.

To evaluate serial changes in renal function by investigating various clinical factors after radical nephrectomy (RN).

Relationships between genetic polymorphisms of triggering receptor expressed on myeloid cells-1 and inflammatory bowel diseases in the Korean population

AIMS Triggering receptor expressed on myeloid cells-1 (TREM-1) has been shown to play a crucial role in the propagation of inflammatory responses. Recent studies have reported that TREM-1 expression is up-regulated in patients with inflammatory bowel disease (IBD). Therefore, we investigated the associations between TREM-1 genetic polymorphisms and IBD development and its phenotypes in the Korean population. MAIN METHODS Three TREM-1 single nucleotide polymorphisms (SNPs, rs2234237, rs3789205, and rs9471535) were genotyped by Taqman technology on 202 Crohns disease (CD), 265 ulcerative colitis (UC), 138 with intestinal Behcets disease (BD), and 234 healthy controls and the relationships between these SNPs and IBD development and phenotypes were evaluated. KEY FINDINGS We found that TREM-1 SNPs are significantly associated with the development of intestinal Behcets disease (rs9471535: odds ratio [OR]=1.637, P=0.025; rs3789205: OR=1.668, P=0.019; rs2234237: OR=1.691, P=0.016), and in particular with skin involvement (rs9471535: OR=2.723, P=0.009; rs3789205: OR=2.477, P=0.017; rs2234237: OR=2.278, P=0.030) and the risk of azathioprine use (rs9471535: OR=2.722, P=0.021; rs3789205: OR=2.493, P=0.032; rs2234237: OR=2.638, P=0.026). However, TREM-1 SNPs were not significantly associated with the development of Crohns disease or ulcerative colitis. SIGNIFICANCE The results of our study suggest that TREM-1 SNPs may play a significant role in the development of intestinal Behcets disease and may have modest effects on disease severity.

Augmentation Index Association With Reactive Hyperemia as Assessed by Peripheral Arterial Tonometry in Hypertension

BACKGROUND Augmentation pressure has emerged as a surrogate marker for cardiovascular disease, and endothelial dysfunction has been proposed as related factor. However, the relationship between augmentation pressure and digital endothelial function has not yet been well defined. We investigated the relationship between augmentation pressure and digital reactive hyperemia (RH) in patients with hypertension using peripheral arterial tonometry (PAT), which is regarded as being representative of endothelial function. METHODS One hundred hypertensive patients (64 males; mean age, 49 ± 12 years) without a history of taking antihypertensive medication were enrolled in this study. RESULTS The mean augmentation pressure and augmentation index (AIx) normalized for a heart rate of 75 beats/min (AIx75) were 15 ± 8 mm Hg and 26 ± 11%, respectively. The mean RH-PAT index and log transformed PAT ratio were 2.24 ± 0.55 and 0.62 ± 0.30. There was an inverse relationship between the RH-PAT index and age, male sex, and body mass index. The log transformed PAT ratio also showed inverse relationship with age and male sex. The RH-PAT index and the log transformed PAT ratio showed no relationship with augmentation pressure or AIx75. In a multiple linear regression analysis, age, height, and central systolic BP demonstrated an independent association with augmentation pressure and AIx75. CONCLUSION In patients with hypertension, the RH-PAT index determined using PAT was not associated with augmentation pressure or AIx75. Digital vascular function may be a less important factor for pressure augmentation in patients with hypertension.

Common variants in RYR1 are associated with left ventricular hypertrophy assessed by electrocardiogram

AIMS To identify the genetic risk factors that influence the development of electrocardiographic (ECG) left ventricular hypertrophy (LVH), a major risk factor for cardiovascular (CV) morbidity and mortality. METHODS AND RESULTS We performed a genomewide association study (GWAS) of ECG-LVH, in which the community-based Korea Association REsource (KARE) study (8432 controls and 398 cases) was analysed by Affymetrix SNP array 5.0. The GWAS results were validated in hospital-based samples (597 controls and 207 cases). Fourteen single-nucleotide polymorphisms (SNPs) in eight genetic loci (5q35.1, 6p22.3-22.1, 8q24.2, 11p15, 11q21-22.1, 14q12, 17q11.2, and 19q13.1) were associated with ECG-LVH in the original GWAS study (P < 1 × 10(-5)). Of these SNPs, 12 were genotyped in the hospital sample. There was consistent association with the 19q13.1 region which contains RYR1 gene. The most significant SNP in the region was rs10500279, which had genomewide significance in the combined GWAS/replication sample [odds ratio = 1.58 (confidence interval: 1.35-1.85), P = 1.0 × 10(-8)]. Mutations in RYR1, which encodes a major Ca(2+) channel in the skeletal muscle, have been reported to correlate with CV diseases. CONCLUSION We performed the first GWAS for ECG-LVH, implicating the skeletal muscle Ca(2+) channel protein RYR1 as a genetic risk factor. These results might increase our understanding of the development of ECG-LVH.

Genetic variants in the IL12B gene are associated with inflammatory bowel diseases in the Korean population

Recent genomic studies have identified genetic variants in the IL12B gene, which encodes the p40 subunit shared by interleukin 12 and interleukin 23, as susceptibility loci for inflammatory bowel disease (IBD). The study aimed to identify additional novel genetic variants in IL12B and investigated whether variants confer susceptibility to the development of Crohns disease (CD) or ulcerative colitis (UC) in the Korean population.

The relationship between insulin-like growth factor-1 and metabolic syndrome, independent of adiponectin

BACKGROUND Insulin-like growth factor-1 (IGF-1) is associated with obesity and aging, and was recently linked to metabolic syndrome (MetS) and insulin resistance. However, little is known about the relationship between IGF-1 and adiponectin (adiponectin), another marker of MetS. METHODS We measured the plasma IGF-1 and adiponectin levels of 3099 subjects (1869 males, 55.9±10.8 y). We applied the Korean-modified International Diabetes Foundation (k-IDF) criteria for determination of, and risk assessment for, MetS. RESULTS K-IDF criteria-based MetS occurred in 37.0% (n=1146) of patients. IGF-1 (91.5 vs. 97.3 ng/ml, p<0.001) and adiponectin (3.95 vs. 4.23 μg/ml, p<0.001) were significantly lower in MetS patients than without MetS. Lower IGF-1 was associated with increasing numbers of MetS abnormalities, independent of adiponectin (p for trend<0.001, F=12.615, p<0.001 in ANCOVA). MetS prevalence in individuals with both high IGF-1 and adiponectin levels (6.7%, n=206) was significantly lower than in other groups. Both high IGF-1 and adiponectin group was associated with reduced MetS risk after adjusting for other confounding factors (OR 0.694, 95% CI 0.493-0.977, p=0.036). CONCLUSIONS IGF-1 was associated with MetS independent of adiponectin in our study. The independent relationship between IGF-1 and MetS provides insight into the pathophysiologic mechanisms of MetS.

Comparison of arterial stiffness indices measured by the Colins and SphygmoCor systems

Arterial stiffness is a known independent predictor of cardiovascular mortality. The Colins system is an easy device and has gained widespread use, but the cutoff value for high-risk central arterial stiffness is not well established. We investigated the correlation between arterial stiffness measured by the Colins system with conventional measurements from the SphygmoCor system. Arterial pulse wave velocity (PWV) and augmentation indices (AIs) were measured on a single visit using two different devices in 948 patients with hypertension or coronary artery disease. Strong positive correlations were observed for PWV values measured by the SphygmoCor and Colins systems. The Colins system measurements accurately predicted high-risk central arterial stiffness, defined as carotid–femoral PWV⩾12 m s−1, with an area under the receiver-operating characteristic curve (AUC) of 0.884 (heart–femoral PWV, hfPWV) and 0.830 (brachial–ankle PWV, baPWV) in the training set (N=664). The cutoff values, 11.18 (hfPWV) and 16.17 m s−1 (baPWV), showed good discrimination in the validation set (N=284), with sensitivity of 83.3 (hfPWV) and 76.0% (baPWV), and specificity of 74.9 (hfPWV) and 82.6% (baPWV). The SphygmoCor and Colins AI systems also showed moderate positive correlation. The Colins AI system better predicted high-risk central pulse pressure as defined by pulse pressure⩾50 mm Hg (AUC: Colins, 0.765; SphygmoCor, 0.692; P=0.011). Arterial stiffness measured by the Colins system showed strong positive correlation and agreement with the SphygmoCor system measurement. Cutoff values for high-risk central arterial stiffness in the Colins system need further validation in a prospective study.

Diagnostic accuracy of narrow band imaging for predicting colon polyp histology can be affected by polyp characteristics.

BACKGROUND/AIMS Narrow band imaging (NBI) is an optical endoscopic technique for predicting polyp histology during colonoscopy. However, it has not been elucidated the impact of polyp characteristics on the diagnostic capabilities of NBI. We aimed to evaluate which polyp characteristics can influence the diagnostic accuracy of NBI for discriminating neoplastic from non-neoplastic colorectal polyps. METHODOLOGY A total of 232 colorectal polyps from 134 patients undergoing screening or surveillance colonoscopy were retrospectively analyzed. White light imaging (WLI) and NBI images of polyps were assessed by two experienced endoscopists and two trainees and then compared with histopathology. RESULTS When classified according to polyp morphology, NBI as well as WLI had a significantly lower sensitivity and diagnostic accuracy for non-polypoid lesions than for polypoid lesions in both experienced and trainee groups. In contrast, the specificity of NBI and WLI for non-polypoid lesions was higher than that for polpyoid lesions. As for polyp size, the diagnostic accuracy of NBI for polyps ≤5mm was significantly lower than for polyps of 6 to 9mm or ≤10mm in the experienced group. CONCLUSIONS NBI had a significantly lower diagnostic accuracy for predicting polyp histology in non-polypoid or diminutive colorectal lesions.