Interaction between ALDH2 rs671 and life habits affects the risk of hypertension in Koreans: A STROBE observational study.

ABSTRACT: Aldehyde dehydrogenase-2 (ALDH2) is associated with the risk of hypertension, and the effects of lifestyle factors on blood pressure vary according to genotype. Among the Han Chinese, the risk of hypertension is lower in the group with the rs671 A allele than in the group with the G allele, and there is a significant association between the frequency of fried food consumption and hypertension. However, the A allele significantly increases the risk of hypertension with increased fried food intake. This study aimed to investigate the effect of the relationship between ALDH2 polymorphism and complex lifestyle habits (fried food consumption and exercise) on hypertension.rs671 polymorphisms of ALDH2 were examined using Korean genome and epidemiology data from 8157 hypertensive cases and 9550 controls. Further, we investigated whether the A allele is protective against hypertension in Koreans and explored the effect of the combination of fried food intake and exercise habits on hypertension by genotype.The genotype frequencies of rs671, which is specific to East Asia, were 2.51% AA, 26.66% GA, and 70.83% GG in the Korean population. The group with inactive aldehyde dehydrogenase-2 had a low odds ratio [OR = 0.75 (95% CI:0.69-0.80), P = 4.35 × 10-14] of hypertension, and low metabolism of acetaldehyde. Subjects carrying the A allele exhibited an increased risk of hypertension with increased fried food intake without exercise [OR = 2.256 (95% CI:1.094-4.654), P = .028].ALDH2 polymorphism and complex lifestyle habits (fried food consumption and exercise) are associated with the risk of hypertension. Further, the A allele is associated with a low risk of hypertension, but it increases the risk of hypertension as fried food intake without exercise increases.

MYLK and PTGS1 Genetic Variations Associated with Osteoporosis and Benign Breast Tumors in Korean Women.

Osteoporosis, characterized by reduced bone mass and increased bone fragility, is a disease prevalent in women. Likewise, breast cancer is a multifactorial disease and considered the major cause of mortality in premenopausal and postmenopausal women worldwide. Our data demonstrated the association of the MYLK gene and PTGS1 gene variants with osteoporosis and benign breast tumor risk and the impact of ovariectomy on osteoporosis in Korean women. We performed a genome-wide association study (GWAS) of women with osteoporosis and benign breast tumors. There were 60 single nucleotide polymorphisms (SNPs) and 12 SNPs in the MYLK and PTGS1 genes, associated with benign breast tumors and osteoporosis. Our study showed that women with homozygous MYLK rs12163585 major alleles had an increased risk of osteoporosis following ovariectomy compared to those with minor alleles. Women carrying the minor PTGS1 rs1213265 allele and not treated via ovariectomy carried a higher risk of osteoporosis than those who underwent ovariectomy with a homozygous genotype at the major alleles. Our results suggest that both the MYLK and PTGS1 genes are genetic factors associated with the phenotypes, and these associations appear to be modulated by ovariectomy.

Dietary Protein and Fat Intake Affects Diabetes Risk with CDKAL1 Genetic Variants in Korean Adults.

Cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) is one of the strongest diabetes loci identified to date; evidence suggests that it plays an important role in insulin secretion. Dietary factors that affect insulin demand might enhance the risk of diabetes associated with CDKAL1 variants. Our aim was to examine the interactions between dietary protein and fat intake and CDKAL1 genetic variants in relation to the risk of diabetes in Korean adults. Single nucleotide polymorphisms (SNPs) were selected with a genome-wide association study (GWAS) for diabetes after adjustment for age, gender, and examination site. Using data from the Health Examinees (HEXA) Study of the Korean Genome and Epidemiology Study (KoGES), 3988 middle-aged Korean adults between 40-76 years of age (2034 men and 1954 women) were included in the study. Finally, rs7756992 located within the CDKAL1 gene region was selected from GWAS (p-value < 5 × 10-8). Multivariable logistic regression models were used to evaluate the interactions between genotypes and dietary protein and fat intake in relation to diabetes risk after adjustment for age, gender, BMI, waist circumference, physical activity, smoking status, drinking habits, and examination site. Significant interactions between CDKAL1 rs7756992 and dietary protein and fat intake for the risk of diabetes were observed in men (p-value < 0.05). In women, significant interactions between dietary protein and fat intake and CDKAL1 variants (rs7756992) were associated with increased risk of diabetes (p-value < 0.05). Dietary protein and fat intake interacted differently with CDKAL1 variants in relation to the risk of diabetes in Korean adults of both genders. These findings indicate that CDKAL1 variants play a significant role in diabetes and that dietary protein and fat intake could affect these associations.

Anti-Osteoporotic Effects of Kukoamine B Isolated from Lycii Radicis Cortex Extract on Osteoblast and Osteoclast Cells and Ovariectomized Osteoporosis Model Mice.

Osteoporosis is an abnormal bone remodeling condition characterized by decreased bone density, which leads to high risks of fracture. Previous study has demonstrated that Lycii Radicis Cortex (LRC) extract inhibits bone loss in ovariectomized (OVX) mice by enhancing osteoblast differentiation. A bioactive compound, kukoamine B (KB), was identified from fractionation of an LRC extract as a candidate component responsible for an anti-osteoporotic effect. This study investigated the anti-osteoporotic effects of KB using in vitro and in vivo osteoporosis models. KB treatment significantly increased the osteoblastic differentiation and mineralized nodule formation of osteoblastic MC3T3-E1 cells, while it significantly decreased the osteoclast differentiation of primary-cultured monocytes derived from mouse bone marrow. The effects of KB on osteoblastic and osteoclastic differentiations under more physiological conditions were also examined. In the co-culture of MC3T3-E1 cells and monocytes, KB promoted osteoblast differentiation but did not affect osteoclast differentiation. In vivo experiments revealed that KB significantly inhibited OVX-induced bone mineral density loss and restored the impaired bone structural properties in osteoporosis model mice. These results suggest that KB may be a potential therapeutic candidate for the treatment of osteoporosis.

High Genetic Risk Scores of ASIC2, MACROD2, CHRM3, and C2orf83 Genetic Variants Associated with Polycystic Ovary Syndrome Impair Insulin Sensitivity and Interact with Energy Intake in Korean Women.

BACKGROUND: We explored the genetic variants that were associated with polycystic ovary syndrome (PCOS) by genome-wide association study (GWAS) and evaluated the association of genetic risk scores (GRS) of the selected genetic variants with insulin resistance and the interaction of the GRS with nutrient intake to develop insulin resistance. METHODS: The 6 genetic variants involved in brain and nervous system (acid sensing ion channel subunit 2 rs8071961, rs1988598, and rs16589, macro domain containing 2 rs7262810 CHRM3 rs1867265 and chromosome 2 open reading frame 83 rs11889798) were selected from a GWAS of the PCOS study. GRS of the 6 single nucleotide polymorphisms was calculated in 3,723 Korean women in the Ansan/Ansung cohort of KARE study. RESULTS: Fasting serum insulin and C-reactive protein (CRP) levels, homeostasis model assessment of insulin resistance (HOMA-IR), and psychological stress levels were significantly higher in the high-GRS group than the low-GRS group. However, serum-free T4 levels were significantly lower in the high-GRS group. HOMA-IR and CRP were higher OR (1.129 and 1.382) in the high-GRS group than the low-GRS group after adjusted for covariates. There was a significant interaction between GRS and daily energy intake (p = 0.004). The OR (1.233) for HOMA-IR was higher in the high-GRS group than the low-GRS group only in the group with lower energy intakes based on estimated energy requirement. CONCLUSION: Women with high-GRS for PCOS had increased risk of insulin resistance and low energy intake did not protect against the elevation of insulin resistance in women with high GRS. Low energy intake might be protective against PCOS in carriers with low and medium GRS.

Transcriptional profiling of human femoral mesenchymal stem cells in osteoporosis and its association with adipogenesis.

Genetic alterations are major contributing factors in the development of osteoporosis. Osteoblasts and adipocytes share a common origin, mesenchymal stem cells (MSCs), and their genetic determinants might be important in the relationship between osteoporosis and obesity. In the present study, we aimed to isolate differentially expressed genes (DEGs) in osteoporosis and normal controls using human MSCs, and elucidate the common pathways and genes related to osteoporosis and adipogenesis. Human MSCs were obtained from the bone marrow of femurs from postmenopausal women during orthopedic surgeries. RNA sequencing (RNA-seq) was carried out using next-generation sequencing (NGS) technology. DEGs were identified using RNA-seq data. Ingenuity pathway analysis (IPA) was used to elucidate the common pathway related to osteoporosis and adipogenesis. Candidate genes for the common pathway were validated with other independent osteoporosis and obese subjects using RT-PCR (reverse transcription-polymerase chain reaction) analysis. Fifty-three DEGs were identified between postmenopausal osteoporosis patients and normal bone mineral density (BMD) controls. Most of the genetic changes were related to the differentiation of cells. The nuclear receptor subfamily 4 group A (NR4A) family was identified as possible common genes related to osteogenesis and adipogenesis. The expression level of the mRNA of NR4A1 was significantly higher in osteoporosis patients than in controls (p=0.018). The expression level of the mRNA of NR4A2 was significantly higher in obese patients than in controls (p=0.041). Some genetic changes in MSCs are involved in the pathophysiology of osteoporosis. The NR4A family might comprise common genes related to osteoporosis and obesity.

Free triiodothyronine/free thyroxine ratio rather than thyrotropin is more associated with metabolic parameters in healthy euthyroid adult subjects.

OBJECTIVE: The interrelation between TSH, thyroid hormones and metabolic parameters is complex and has not been confirmed. This study aimed to determine the association of TSH and thyroid hormones in euthyroid subjects and the relationship between thyroid function and metabolic risk factors. Furthermore, this study examined whether thyroid function has predictive power for metabolic syndrome. DESIGN: This is a cross-sectional study that included subjects in a medical health check-up programme at a single institution. PATIENTS: The study included 132 346 participants (66 991 men and 65 355 women) aged over 18 years who had TSH, free T4 (FT4) and free T3 (FT3) levels within the institutional reference ranges. MEASUREMENTS: Thyrotropin, FT4, FT3 and metabolic parameters including height, weight, waist circumference, blood pressure, serum levels of total cholesterol, triglyceride, high-density lipoprotein cholesterol, insulin and glucose were measured. RESULTS: There was a positive association between FT3/FT4 ratio and TSH in both men and women after adjusting for age, body mass index, smoking status and menopausal status (in women). The FT3/FT4 ratio and TSH were positively associated with risk of metabolic syndrome parameters including insulin resistance. The FT3/FT4 ratio had a greater predictive power than TSH for metabolic syndrome in both men and women. CONCLUSIONS: Thyrotropin levels were positively associated with FT3/FT4 ratio within the euthyroid range. The higher FT3/FT4 ratio is associated with increased risk of metabolic syndrome parameters and insulin resistance. FT3/FT4 ratio has a better predictive power for metabolic syndrome than TSH.

Identification of a Novel Mutation in BRD4 that Causes Autosomal Dominant Syndromic Congenital Cataracts Associated with Other Neuro-Skeletal Anomalies.

Congenital cataracts can occur as a non-syndromic isolated ocular disease or as a part of genetic syndromes accompanied by a multi-systemic disease. Approximately 50% of all congenital cataract cases have a heterogeneous genetic basis. Here, we describe three generations of a family with an autosomal dominant inheritance pattern and common complex phenotypes, including bilateral congenital cataracts, short stature, macrocephaly, and minor skeletal anomalies. We did not find any chromosomal aberrations or gene copy number abnormalities using conventional genetic tests; accordingly, we conducted whole-exome sequencing (WES) to identify disease-causing genetic alterations in this family. Based on family WES data, we identified a novel BRD4 missense mutation as a candidate causal variant and performed cell-based experiments by ablation of endogenous BRD4 expression in human lens epithelial cells. The protein expression levels of connexin 43, p62, LC3BII, and p53 differed significantly between control cells and cells in which endogenous BRD4 expression was inhibited. We inferred that a BRD4 missense mutation was the likely disease-causing mutation in this family. Our findings may improve the molecular diagnosis of congenital cataracts and support the use of WES to clarify the genetic basis of complex diseases.

Interactions with the MC4R rs17782313 variant, mental stress and energy intake and the risk of obesity in Genome Epidemiology Study.

BACKGROUND: The melanocortin-4 receptor (MC4R) regulates metabolism by modulating eating behavior and MC4R variants (rs17782313 and rs571312) are associated with obesity in Asians and Caucasians. However, the impact of their interactions with nutritional and lifestyle factors on obesity are poorly described. Therefore, we investigated the interaction of MC4R variants and dietary patterns on the risk of obesity in Korean middle-aged adults. METHODS: Data collected included, genetic variations, anthropometric and biochemical measurements, dietary and lifestyle habits, and food intake. Data were obtained from the 8830 adults aged 40-69 years in the Ansung and Ansan cohort of the Korean Genome Epidemiology Study. RESULTS: The MC4R rs18882313 minor allele had a higher frequency in the obese group (P < 0.01). MC4R genotypes were not associated with differences in daily energy and macronutrient intakes. However, the intakes of processed foods and fat (as percentages of energy) were significantly higher and intake of fruits were significantly lower in subjects with MC4R minor alleles (P < 0.05). Interestingly, there was a positive interaction between MC4R variants and mental stress levels that were associated with the risk of obesity after adjusting for age, gender, residence area, daily energy intake, smoking status and physical activity (interaction P = 0.0384). Only in subjects with high stress were MC4R minor alleles associated with higher BMIs after adjusting for confounders. The association was present without modulating energy and nutrient intake. In the group with energy intakes higher than estimated energy requirement (EER), subjects with MC4R minor alleles had higher BMIs than those with the major alleles (P < 0.001). CONCLUSIONS: The interactions of mental stress and energy intakes with the MC4R minor allele genotype might be associated with increased risk of obesity in Korean adults. This research might identify subjects with a specific MC4R minor alleles as a human subset of people with a low metabolic tolerance for excessive energy intake, especially when under stress.

Association of the I264T variant in the sulfide quinone reductase-like (SQRDL) gene with osteoporosis in Korean postmenopausal women.

To identify novel susceptibility variants for osteoporosis in Korean postmenopausal women, we performed a genome-wide association analysis of 1180 nonsynonymous single nucleotide polymorphisms (nsSNPs) in 405 individuals with osteoporosis and 722 normal controls of the Korean Association Resource cohort. A logistic regression analysis revealed 72 nsSNPs that showed a significant association with osteoporosis (p<0.05). The top 10 nsSNPs showing the lowest p-values (p = 5.2×10-4-8.5×10-3) were further studied to investigate their effects at the protein level. Based on the results of an in silico prediction of the protein's functional effect based on amino acid alterations and a sequence conservation evaluation of the amino acid residues at the positions of the nsSNPs among orthologues, we selected one nsSNP in the SQRDL gene (rs1044032, SQRDL I264T) as a meaningful genetic variant associated with postmenopausal osteoporosis. To assess whether the SQRDL I264T variant played a functional role in the pathogenesis of osteoporosis, we examined the in vitro effect of the nsSNP on bone remodeling. Overexpression of the SQRDL I264T variant in the preosteoblast MC3T3-E1 cells significantly increased alkaline phosphatase activity, mineralization, and the mRNA expression of osteoblastogenesis markers, Runx2, Sp7, and Bglap genes, whereas the SQRDL wild type had no effect or a negative effect on osteoblast differentiation. Overexpression of the SQRDL I264T variant did not affect osteoclast differentiation of the primary-cultured monocytes. The known effects of hydrogen sulfide (H2S) on bone remodeling may explain the findings of the current study, which demonstrated the functional role of the H2S-catalyzing enzyme SQRDL I264T variant in osteoblast differentiation. In conclusion, the results of the statistical and experimental analyses indicate that the SQRDL I264T nsSNP may be a significant susceptibility variant for osteoporosis in Korean postmenopausal women that is involved in osteoblast differentiation.

Identification of KMT2D and KDM6A mutations by exome sequencing in Korean patients with Kabuki syndrome.

Kabuki syndrome (KS) (OMIM#147920) is a multiple congenital anomaly/mental retardation syndrome. Recently, pathogenic variants in KMT2D and KDM6A were identified as the causes of KS in 55.8-80.0% of patients. To elucidate further the molecular characteristics of Korean patients with KS, we screened a cohort of patients with clinically defined KS for mutations in KMT2D and KDM6A. Whole-exome sequencing and direct sequencing for validation were performed in 12 patients with a clinical suspicion of KS. KMT2D and KDM6A mutations were identified in 11 (91.7%) patients. No recurrent mutation was observed, and 10 out of the 11 mutations found were novel. KMT2D mutations were detected in 10 patients, including four small deletions or insertions and four nonsense and two missense mutations. One girl had a novel splice-site mutation in KDM6A. Each patient had a unique individual mutation. This is the first report of mutational analysis via exome sequencing in Korean patients with KS. Because the mutation-detection rate was high in this study, rigorous mutation analysis of KMT2D and KDM6A may be an important tool for the early diagnosis and genetic counseling of Korean patients with KS.

The PARK2 gene is involved in the maintenance of pancreatic ß-cell functions related to insulin production and secretion.

Several association studies have implicated the PARK2 gene that encodes parkin--the key molecule orchestrating the mitochondrial quality control system--as a candidate susceptibility gene for diabetes. A total of 7551 unrelated Korean KARE cohort subjects were analyzed to investigate the association between the PARK2 single nucleotide polymorphism (SNP) and quantitative glycemic traits. Two SNPs, rs10455889 and rs9365294, were significantly associated with fasting plasma glucose level (p=∼1.2×10(-4)) and insulin secretion indices (p=∼7.4×10(-5)) in male KARE subjects. Parkin was expressed predominantly in the rat pancreatic islets. Downregulation of the Park2 gene in rat INS-1 ß-cells resulted in a significant decrease in the glucose-stimulated insulin secretion, intracellular insulin gene expression, and intracellular ATP level. The Park2-depleted ß-cells also exhibited increased mitochondrial fragmentation and ROS production and decreased mitochondrial membrane potential. Both population-based statistical evaluation and experimental evidence demonstrated a fundamental role of the PARK2 gene in the maintenance of ß-cell function.

NF1 deficiency causes Bcl-xL upregulation in Schwann cells derived from neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors.

Since the bi-allelic inactivation of both neurofibromin 1 (NF1) gene alleles (NF1(-/-)) in Schwann cells (SCs) is common in both benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) in patients with neurofibromatosis type 1 (NF1), other genetic alterations in SCs may be required for tumor progression of PNs to MPNSTs. We found that the anti-apoptotic Bcl-xL protein is upregulated in MPNST tissues compared to PN tissues from patients with NF1 by immunohistological staining. In addition, we investigated whether Bcl-xL is upregulated in SCs derived from MPNSTs and found a significantly higher Bcl-xL expression level in sNF96.2 MPNST-derived SCs compared to normal human SCs (HSCs). We also discovered that the increased Bcl-xL expression caused an increase in drug resistance to doxorubicin in MPNST-derived SCs. Manipulation of NF1 gene expression levels by treatment with small interfering RNA (siRNA) and overexpression of the neurofibromin GAP-related domain (NF1-GRD) demonstrated that upregulated Bcl-xL expression in MPNST-derived SCs was caused by NF1 deficiency. Treatment with the Erk1/2 inhibitor, PD98059, resulted in a slight increase in Bcl-xL levels in neurofibromin-depleted normal HSCs, indicating that Bcl-xL upregulation in MPNST-derived SCs is mediated by activated Erk1/2, which is a Ras downstream protein regulated by neurofibromin. As the reduction of Bcl-xL expression restored sensitivity to doxorubicin-induced apoptosis in sNF96.2 cells, we examined the effect of the small molecule Bcl-xL inhibitor ABT-737 on sNF96.2 cells. A very low dose of ABT-737 combined with doxorubicin synergistically enhanced sensitivity to doxorubicin-induced apoptosis in sNF96.2 cells, suggesting that ABT-737 and doxorubicin may be a good combination to effectively treat NF1-associated MPNSTs with minimal side-effects. Collectively, our results suggest that upregulation of Bcl-xL in MPNST-derived SCs may be caused by the NF1 deficiency-mediated elevation in Ras/MAPK signaling and may provide a new potential chemotherapeutic target in patients with NF1 and MPNSTs.

Genome-wide association study of serum albumin:globulin ratio in Korean populations.

Low albumin:globulin (A/G) ratios are associated with vascular adverse events, nephrotic syndrome and autoimmune disease. Genome-wide association studies (GWASs) have been identifying genetic variants associated with total serum protein, serum albumin and globulins, but A/G ratio has never been considered the target phenotype. To identify the genetic basis of the A/G ratio, we performed a GWAS on A/G ratio in 4205 individuals from the Ansan cohort and confirmed the results in 4637 subjects from the Ansung cohort. The single-nucleotide polymorphism (SNP) genotypes of Affymetrix SNP array 5.0 were obtained from the Korean Association Resource Consortium, and we selected 290 659 common SNPs with a minor allele frequency >0.05. Genetic factors for A/G ratio were analyzed by linear regression analysis, controlling for age, sex, body mass index, smoking status and alcohol drinking status as covariates. From the GWAS of the Ansan cohort, we identified two significant genome-wide signals (P-values<5 × 10(-8)) and 36 moderate signals (P-value<1.0 × 10(-4)). These 38 signals were tested in the Ansung population. Eleven SNPs from six loci (GALNT2, IRF4, HLA-DBP1, SLC31A1, FADS1 and TNFRSF13B) were replicated, with P-values<0.05. The most compelling association was observed in the TNFRSF13B locus on chromosome 17p11.2 (SNP: rs4561508), with an overall combined P-value=7.80 × 10(-24). The other significant signal was observed on chromosome 11q12.2-the FADS1 locus (SNP: rs174548)-with an overall combined P-value=3.54 × 10(-8).

Inhibition of Bcl-xL by ABT-737 enhances chemotherapy sensitivity in neurofibromatosis type 1-associated malignant peripheral nerve sheath tumor cells.

Neurofibromatosis type 1 (NF1) is one of the most commonly inherited autosomal dominant disorders. The malignant peripheral nerve sheath tumor (MPNST) is a major cause of mortality in patients with NF1. In this study, we found that overexpression of Bcl-xL in the established NF1-associated MPNST cell line and primary tissue cultured MPNST cells derived from an NF1 patient was closely associated with anticancer drug resistance of the NF1-associated MPNST cells. We demonstrated that high expression of Bcl-xL in the MPNST cells was caused by a decreased transcriptional expression of the NF1 gene. Downregulation of the NF1 gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and primary normal cells. These results suggest that an alteration of Bcl-xL expression levels by somatic expression changes in the NF1 locus may contribute to the malignant development of benign tumor tissues or normal tissues to MPNSTs. We further demonstrated that either depletion of Bcl-xL expression by RNAi or inactivation of Bcl-xL by ABT-737, a mimetic of the BH3-only protein BAD, was very effective in sensitizing the MPNST cells to apoptotic cell death by combined treatment with the tested anticancer drug doxorubicin. Notably, a low concentration of ABT-737 and doxorubicin could effectively induce synergistic cytotoxicity in the MPNST cells. These results suggest that pharmacological inhibition of Bcl-xL by ABT-737 in combination with doxorubicin can be a potential therapeutic strategy for the treatment of NF1-associated MPNSTs.

Association between renin-angiotensin-aldosterone system-related genes and blood pressure in a Korean population.

AIMS. Blood pressure control is influenced by various genetic and environmental factors, and genetic susceptibility is important in the development of essential hypertension. Because the renin-angiotensin-aldosterone system (RAAS) has a key role in vasoconstriction, vasodilation, and sodium and electrolyte balance, it is central in blood pressure control and so is an appropriate target in hypertension treatments. The present study assessed the association of RAAS-related genes with blood pressure and hypertension in a Korean population. Single nucleotide polymorphisms (SNPs, n = 114) in nine RAAS-related genes (AGT, REN, ACE, ACE2, AGTR1, CYP11B2, NR3C2, MAS1, and CMA1) were assessed for their correlation with blood pressure and hypertension using genotype data of 8842 individuals from the Korea Association Resource subject pool. MAJOR FINDINGS. Linear regression analysis revealed a statistically significant association with blood pressure of 10 SNPs in six genes (ACE, ACE2, CYP11B2, NR3C2, MAS1, and CMA1). An additional hypertension case-control study identified 10 SNPs in NR3C2 and ACE that were linked to hypertension. PRINCIPAL CONCLUSION. Three SNPs (rs11737660, rs6810951, and rs10519963) in NR3C2 correlate with both blood pressure and hypertension. Genetic polymorphisms in RAAS-related genes appear to be associated with hypertension in a Korean population.

A biomechanical comparison of vertical figure-of-eight locking suture for septal extension grafts.

Septal extension grafts are performed in order to correct the conformation of the nasal tip and columella. The more strongly the graft is fixed to the columellar L-strut of the septal cartilage, the better is the outcome of grafting. This article reports the development of a vertical figure-of-eight locking suture technique and its biomechanical comparison with other suture techniques. Pieces of porcine rib cartilage 20 x 15 x 1 mm (or 2 mm) in size were used for the study. Two pieces of cartilage were fixed using two simple interrupted sutures in the first group, two horizontal figure-of-eight locking sutures in the second group and the vertical figure-of-eight locking suture in the third group. Shearing, buckling and tensile forces were measured with respect to the direction of forces that occur in vivo. The mean shearing force for cartilages that were 1 mm in thickness was 0.70, 0.74 and 1.04 N (P=0.056) in the first, second and third group, respectively. The mean buckling force was 1.10, 1.09 and 1.39 N (P=0.030), and the mean tensile force was 1.86, 1.78 and 2.24 (P=0.042), respectively. For cartilages that were 2 mm in thickness, the mean shearing force was 1.19, 1.29 and 1.54 N (P=0.216), the mean buckling force was 1.74, 1.50 and 2.25 (P=0.002) and the mean tensile force was 2.00, 1.81 and 2.29 (P=0.023) in the first, second and third group, respectively. The vertical figure-of-eight locking suture technique was developed as an alternative technique for suturing a septal extension graft to the columellar L-strut, and it enables firm fixation with the use of the fewest number of stitches.