Beyoung Yun Park

Association between IRF6 and nonsyndromic cleft lip with or without cleft palate in four populations

Purpose: The interferon regulatory factor 6 (IRF6), the gene that causes van der Woude syndrome has been shown to be associated with nonsyndromic cleft lip with or without palate in several populations. This study aimed to confirm the contribution of IRF6 to cleft lip with or without palate risk in additional Asian populations.Methods: A set of 13 single nucleotide polymorphisms was tested for association with cleft lip with or without palate in 77 European American, 146 Taiwanese, 34 Singaporean, and 40 Korean case-parent trios using both the transmission disequilibrium test and conditional logistic regression models.Results: Evidence of linkage and association was observed among all four populations; and two specific haplotypes [GC composed of rs2235373-rs2235371 (p.V274I) and AAG of rs599021-rs2235373-rs595918] showed the most significant over- and undertransmission among Taiwanese cases (P = 9 × 10−6 and P = 5 × 10−6, respectively). The AGC/CGC diplotype composed of rs599021-rs2235373-rs2013162 showed almost a 7-fold increase in risk among the Taiwanese sample (P < 10−3). These results confirmed the contribution of this gene to susceptibility of oral clefts across different populations; however, the specific single nucleotide polymorphisms showing statistical significance differed among ethnic groups.Conclusion: The high-risk genotypes and diplotypes identified here may provide a better understanding of the etiological role of this gene in oral clefts and potential options for genetic counseling.

Objective evaluation of treatment effects on port-wine stains using L*a*b* color coordinates.

Wide variations in port‐wine stains and their responses to various therapies pose a need for the development of an objective method to evaluate the effects of treatment. Several techniques such as laser Doppler, reflectance spectrometry, and tristimulus colorimetry have been used to evaluate the color of port‐wine stains, but these techniques are limited by cost, small test size area, and other factors. Therefore, we developed a simple and cost‐effective method of evaluating treatment results on port‐wine stains using the L*a*b* color coordinate system in combination with a personal computer. For 22 patients with port‐wine stains, the slide photographs were digitized using a slide scanner. L*a*b* color differences of the normal control and port‐wine stain sites were obtained before and after treatment, and treatment effect (percent) was calculated. By calculating each color difference between the lesion and normal skin both before and after treatment, problems arising from different illuminating conditions during photography were minimized. The results were compared with the visual evaluation conducted by three experienced plastic surgeons. The treatment effects analyzed by L*a*b* color coordinate ranged from 4 to 95 percent, with a mean of 48.1 percent, whereas treatment effects evaluated by the plastic surgeons ranged from 15 to 92 percent, with a mean of 51.1 percent. The subjective clinical grades correlated well with the treatment effects obtained by the proposed color analysis system (correlation coefficient, 0.89). The maximum difference in the effect of treatment for a patient evaluated by the three clinicians was up to 60 percent, which means that visual judgment is very subjective and variable. The color analysis system proposed as a result of this study is very easy, objective, quantitative, cost‐effective, and can be useful for the evaluation of treatment effects on colored skin lesions such as port‐wine stains. (Plast. Reconstr. Surg. 108: 842, 2001.)

Differential parental transmission of markers in RUNX2 among cleft case-parent trios from four populations

Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence around 1 in 700 live births. The Runt‐related transcription factor 2 (RUNX2) gene has been suggested as a candidate gene for CL/P based largely on mouse models; however, no human studies have focused on RUNX2 as a risk factor for CL/P. This study examines the association between markers in RUNX2 and isolated, nonsyndromic CL/P using a case‐parent trio design, while considering parent‐of‐origin effects. Case‐parent trios from four populations (77 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 24 single nucleotide polymorphisms (SNPs) in the RUNX2 gene. We performed the transmission disequilibrium test on individual SNPs. Parent‐of‐origin effects were assessed using the transmission asymmetry test and the parent‐of‐origin likelihood ratio test (PO‐LRT). When all trios were combined, the transmission asymmetry test revealed a block of 11 SNPs showing excess maternal transmission significant at the P<0.01 level, plus one SNP (rs1934328) showing excess paternal transmission (P=0.002). For the 11 SNPs showing excess maternal transmission, odds ratios of being transmitted to the case from the mother ranged between 3.00 and 4.00. The parent‐of‐origin likelihood ratio tests for equality of maternal and paternal transmission were significant for three individual SNPs (rs910586, rs2819861, and rs1934328). Thus, RUNX2 appears to influence risk of CL/P through a parent‐of‐origin effect with excess maternal transmission. Genet. Epidemiol. 2008.

Maternal transmission effects of the PAX genes among cleft case–parent trios from four populations

Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of 1 in 700 live births. The paired box (PAX) genes have been suggested as candidate genes for CL/P based largely on mouse models; however, few human studies have focused on this gene family. This study tests for association between markers in four PAX genes and CL/P using a case-parent trio design considering parent-of-origin effects. Trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 34 single nucleotide polymorphisms (SNPs) in the PAX3, PAX6, PAX7, and PAX9 genes. We performed the transmission disequilibrium test (TDT) on individual SNPs. Parent-of-origin effects were assessed using the transmission asymmetry test (TAT) and the parent-of-origin likelihood ratio test (PO-LRT). TDT analysis showed one SNP (rs766325) in PAX7 yielding evidence of linkage and association when parent-of-origin was not considered, with an OR(transmission)=1.62 (P=0.003), and five SNPs in PAX6 (including two pairs in near perfect linkage disequilibrium). TAT analysis of all trios revealed two SNPs in PAX7 and four SNPs in PAX3 showing significant excess maternal transmission. For these six SNPs, the maternal OR(transmission) ranged between 1.74 and 2.40, and PO-LRT was also significant (P-values=0.035–0.012). When this analysis was limited to trios with male cases, SNPs in PAX7 showed higher maternal OR(transmission) and greater significance. PAX genes may influence the risk of CL/P through maternal effects, possibly imprinting, which seems to be stronger among male cases.

Long-term evaluation of elongating columella using conchal composite graft in bilateral secondary cleft lip and nose deformity.

Background: A short columella is one of the most severe problems in bilateral cleft lip and nose deformity. In particular, with tissue insufficiency or scar contracture on the upper lip, it is very hard to achieve a good nasal profile with conventional methods. Methods: One hundred thirty-seven patients with a short columella were operated on from February of 1987 to December of 2008. The average age at operation was 7.3 years. The conchal cartilage was harvested. The preauricular or postauricular skin-subcutaneous fat composite tissue was harvested. Through a transcolumellar incision, the conchal cartilage was inset and the defect was covered with skin-fat composite tissue. The serial nasal profiles were evaluated before and after surgery. Also, the postoperative nasal profiles were compared with normal profiles. The postoperative color difference with surrounding skin was measured by the L*a*b* photographic analysis method. Results: The mean height and width of skin-subcutaneous fat composite tissue were 9.81 and 22.14 mm, respectively. The preoperative and postoperative measuring for columella height was 5.1 ± 1.1 mm and 14.2 ± 1.5 mm. The columella-lip angle was 120.30 ± 12.97 preoperatively degrees and 98.76 ± 10.98 degrees postoperatively, whereas the angle of columellar-alar triangle was 111.56 ± 11.39 degrees and 97.91 ± 11.49 degrees, respectively. None of the postoperative profiles were different from those of normal Korean people of the same age except in the 0- to 6-year-old group (p < 0.05). The color match was best with preauricular composite tissue. Complications included total necrosis in three cases and partial necrosis in 12 cases that were treated conservatively. Conclusion: Elongating columella using a composite graft can be a satisfying alternative, especially for a severe short columella with upper lip tissue deficiency.

MSX1 Polymorphism Associated with Risk of Oral Cleft in Korea: Evidence from Case-Parent Trio and Case-Control Studies

Orofacial clefts, including cleft lip with or without palate (CL/P) and cleft palate (CP), are one of the most common congenital malformations in Asian populations, where the rate of incidence is higher than in European or other racial groups. A number of candidate genes have been identified for orofacial clefts, although no single candidate has been consistently identified in all studies. We performed case-parent trio and case-control studies on 6 single nucleotide polymorphisms (SNPs) in the MSX1 gene using a sample of 52 CL/P and CP probands from Korea. In the case-control study, the allele frequencies of 6 MSX1 SNPs were compared between 52 oral cleft cases and 96 unmatched controls. For the case-parent trio study, single-marker and haplotype-based tests of transmission disequilibrium using allelic and genotypic tests revealed significant evidence of linkage in the presence of disequilibrium for 1170 G/A of exon 2. With the GG genotype as a reference group among GG, GA, and AA genotypes at 1170G/A, the disease risk decreased with the presence of the A allele (AA genotype: OR = 0.26, 95% CI = 0.10-0.99). These results are consistent with evidence from other studies in the US and Chile and confirm the importance of the MSX1 genotype in determining the risk of CL/P and CP in Koreans.

Protection of rabbit kidney from ischemia/reperfusion injury by green tea polyphenol pretreatment

Reactive oxygen species (ROS) have been implicated in the pathogenesis of renal injury after ischemia/reperfusion (I/R). Recently, green tea polyphenols (GTP) have been found to protect the myocardium and liver against I/R injury. Less attention, however, has been paid to the protective effects of GTP with respect to the kidneys. This study was designed to determine whether GTP could protect renal cells from ischemic injury. The rabbits were divided into three groups of equal size: control (sham-operated), I/R + vehicle (normal saline) and I/R + GTP groups. Each group consisted of six rabbits. Animals underwent 30, 60, 90 and 120 min of ischemia, followed by 24 h of reperfusion, respectively. GTP (200 μg/kg) or the vehicle was administered 45 min prior to commencement of I/R. The results demonstrated that GTP administration resulted in a significant (P < 0.05) reduction of renal damage after 90 min of ischemia, as indicated by the decreased levels of creatinine and urea nitrogen in serum. These results were confirmed by histological examinations, which showed that GTP pretreatment inhibited necrosis and sloughing of the proximal tubules induced by I/R. Examinations also showed decreased necrotic areas in the medulla and decreased glomerular collapse in the I/R-injured rabbits. Moreover, the infiltration of CD8+ T cells was considerably decreased in GTP-treated kidneys. The results of this study suggest that GTP can reduce renal injury by preventing the oxidative stress dependent on I/R and may be used in renal transplantation as an antioxidant.

Volume and distances of the maxillary sinus in craniofacial deformities with midfacial hypoplasia

Objective: Craniofacial deformities (CFDs) frequently accompany midfacial hypoplasia. The authors evaluated characteristics of maxillary sinuses that had CFDs with variable degrees of midfacial hypoplasia. Study Design: Cross-sectional survey with chart review. Setting: Department of Plastic and Reconstructive Surgery, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea. Subjects and Methods: We investigated 40 patients with CFDs having midfacial hypoplasia. Study group 1 (SG 1) consisted of eight patients with Crouzon syndrome (16 maxillary sinuses). Study group 2 (SG 2) consisted of 10 patients with midfacial hypoplasia after palatoplasty (20 maxillary sinuses). Study group 3 (SG 3) consisted of 22 patients with Pruzansky grade I hemifacial microsomia (22 maxillary sinuses on the affected sides). Data on volume and three-dimensional distances (height, width, and depth) from computed tomography were collected and compared with each corresponding control group. Correlation coefficient between volume and the three distances was also calculated. Results: The volume, height, width, and depth of the maxillary sinus were significantly decreased in SG 1 (P < 0.01). In SG 2, only the depth was significantly decreased (P < 0.05). In SG 3, there were no significant differences in any parameters. A multiple-regression analysis between the volume and the three distances showed a statistically significant relationship for width in SG 1, width and height in SG 2, and all distances in SG 3. Conclusion: There were differences in the structure of the maxillary sinuses among patients with different CFDs.

Resection of the Prominent Mandible Angle with Intraoral and External Approach

Surgical resection of the prominent mandible angle is a common aesthetic procedure in Asian women. Many females want to change their square-shaped face to a round-shaped face, because the square-shaped face is, not considered attractive in Asian culture. Several approaches have been used for this procedure. Surgeons usually have used the intraoral approach because it can avoid the external scar. However, the intraoral approach can have many drawbacks due to the limited operative field and view. In particular, subcondyle fracture occurs more easily because of the limited motion of the saw. This article presents an operative method that avoids subcondyle fracture and makes the procedure easier to execute. The procedure has two main differences; one is the addition of an external stab incision to the conventional intraoral incision and the other is the use of the reciprocating saw instead of the oscillating saw. Forty-three patients were operated on and we recommend this procedure as an easier procedure with less complication than the intraoral-only approach.

Differential parental transmission of markers in BCL3 among Korean cleft case-parent trios.

OBJECTIVES Isolated cleft lip with or without cleft palate (CL/P) is among the most common human birth defects, with a prevalence of approximately 1 in 700 live births. The B-Cell Leukemia/lymphoma 3 (BCL3) gene has been suggested as a candidate gene for CL/P based on association and linkage studies in some populations. This study tests for an association between markers in BCL3 and isolated, non-syndromic CL/P using a case-parent trio design, while considering parent-of-origin effects. METHODS Forty case-parent trios were genotyped for two single nucleotide polymorphisms (SNPs) in the BCL3 gene. We performed a transmission disequilibrium test (TDT) on individual SNPs, and the FAMHAP package was used to estimate haplotype frequencies and to test for excess transmission of multi-SNP haplotypes. RESULTS The odds ratio for transmission of the minor allele, OR (transmission), was significant for SNP rs8100239 (OR=3.50, p=0.004) and rs2965169 (OR=2.08, p=0.027) when parent-of-origin was not considered. Parent-specific TDT revealed that SNP rs8100239 showed excess maternal transmission. Analysis of haplotypes of rs2965169 and rs8100239 also suggested excess maternal transmission. CONCLUSIONS BCL3 appears to influence risk of CL/P through a parent-of-origin effect with excess maternal transmission.