Total Hip Arthroplasty: Past, Present, and Future. What Has Been Achieved?

In the 1960s, Sir John Charnley introduced to clinical practice his concept of low-friction total hip arthroplasty (THA). Although early designs were plagued by poor performance and even failure, there have been steady advances in implant designs, biomaterials, surgical techniques and an understanding of the biomechanical restoration of the hip; these advances have contributed to improvements in implant survival and clinical outcomes of THA in the past three decades. With improved wear resistance and mechanical reliability, a potential to last for at least 25 to 30 years are now available for THA. In this review, we focus on the evolution of THA and review current controversies and future directions of this procedure based on a single surgeon's 29-year of experience at a single institution.

Comparison of the Effect of Continuous Femoral Nerve Block and Adductor Canal Block after Primary Total Knee Arthroplasty.

BACKGROUND: This study aimed to compare the effects of femoral nerve block and adductor canal block on postoperative pain, quadriceps strength, and walking ability after primary total knee arthroplasty. METHODS: Between November 2014 and February 2015, 60 patients underwent primary total knee arthroplasty. Thirty patients received femoral nerve block and the other 30 received adductor canal block for postoperative pain control. Before spinal anesthesia, the patients received nerve block via a catheter (20 mL 0.75% ropivacaine was administered initially, followed by intermittent bolus injection of 10 mL 0.2% ropivacaine every 6 hours for 3 days). The catheters were maintained in the exact location of nerve block in 24 patients in the femoral nerve block group and in 19 patients in the adductor canal block group. Data collection was carried out from these 43 patients. To evaluate postoperative pain control, the numerical rating scale scores at rest and 45° flexion of the knee were recorded. To evaluate quadriceps strength, manual muscle testing was performed. Walking ability was assessed using the Timed Up and Go test. We also evaluated analgesic consumption and complications of peripheral nerve block. RESULTS: No significant intergroup difference was observed in the numerical rating scale scores at rest and 45° flexion of the knee on postoperative days 1, 2, 3, and 7. The adductor canal block group had significantly greater quadriceps strength than did the femoral nerve block group, as assessed by manual muscle testing on postoperative days 1, 2, and 3. The 2 groups showed no difference in walking ability on postoperative day 1, but on postoperative days 2, 3, walking ability was significantly better in the adductor canal block group than in the femoral nerve block group. No significant intergroup difference was observed in analgesic consumption. CONCLUSIONS: The groups showed no difference in postoperative pain control. Adductor canal block was superior to femoral nerve block in preserving quadriceps strength and walking ability. However, adductor canal block was inferior to femoral nerve block in maintaining the exact location of the catheter.

Osteoconductivity of porous polyethylene in human skull.

PURPOSE: Recently, biomaterials have been generally used in reconstruction of a bony defect or augmentation of the facial skeleton. Medpor implants in vivo in animal models showed both soft tissue and bony ingrowth into its pores and have been widely accepted to have an osteoconduction activity. However, in an in vivo study in humans, there was no definite evidence of bony ingrowth into the pores of Medpor. This study examined the osteoconductivity of Medpor in human vivo. METHODS: We gained a total of 24 Medpor blocks when removing a distraction device in 11 patients with craniosynostosis. The Medpor blocks were used for secure placement of the distraction device. The blocks were taken out after distraction and consolidation periods. The surface of Medpor in contact with the bone was histologically examined to confirm the osteogenic activity. RESULTS: There was no evidence of osteoconduction in all 24 specimens. The mean total duration of implantation was 2.5 months. CONCLUSIONS: In human vivo, implantation of a porous polyethylene implant is thought to have no osteogenetic effect through osteoconductive activity even in young children.

Salvage of expanded skin flap perforation and infection after total ear reconstruction with autogenous costal cartilage.

INTRODUCTION: This study was intended to present methods for salvage perforation and infection of an expended skin flap in total ear reconstruction with autogenous costal cartilage. METHODS: Between March 2008 and March 2009, 5 patients experienced complications (perforation and infection) after total ear reconstruction. The skin perforations were noted between 29 and 100 days after inflation. Continuous irrigation and suction drainage, local flap transposition, and pillow suturing were used to control the perforation and infection. Continuous irrigation and suction drainage, especially, should be maintained until ascertaining a negative conversion of the wound culture. RESULTS: Perforation and infection of the reconstructed ear with an expanded skin flap healed successfully using continuous irrigation and suction drainage, local flap transposition, and pillow suturing. DISCUSSION: We suggest that continuous irrigation and suction drainage with only minimal debridement of grafted autogenous costal cartilage could be satisfactory solutions for salvaging total ear reconstruction after complications.

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 + or - 1.1 mm and 14.2 + or - 1.5 mm. The columella-lip angle was 120.30 + or - 12.97 preoperatively degrees and 98.76 + or - 10.98 degrees postoperatively, whereas the angle of columellar-alar triangle was 111.56 + or - 11.39 degrees and 97.91 + or - 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.

Aesthetic effect of silicone gel on surgical scars in Asians.

BACKGROUND: Scars on exposed areas are a major concern among Asian populations because of their conspicuousness. Size, color, or whether the scar is hypopigmented or hyperpigmented matters little. Silicone gel is well known for the prevention and induction of better maturation of hypertrophic and keloid scars. However, its aesthetic effect on normal surgical scars has not been considered. METHODS: Clinical evaluation of scars was performed in 40 patients. All the 40 patients underwent clean and minor surgery of the exposed area, such as scar revision, by 1 plastic surgeon. Twenty of the 40 patients did not apply any adjunctive material for scar management and were grouped as the control. The other 20 patients applied a silicone gel sheet for 12 hours a day for 3 months. Three assessment criteria, pigmentation, vascularity, and height, were evaluated by photographic assessment of the scars at 2 weeks, 1 month, and 3 months postoperatively and scored by 3 plastic surgeons. The Wilcoxon rank sum test was used to verify any significant differences in the previously mentioned 3 parameters between the 2 groups and parameter scores at each follow-up period. RESULTS: Two patients were excluded from the study because of the development of rashes on the areas covered by the silicone gel sheet. There was no statistical significance between the groups at postoperative 2 weeks and 1 month in pigmentation and redness. For evaluation of height, there was statistical significance (P = 0.024) at postoperative 1 month. However, there were statistically significant differences in all the assessment criteria at postoperative 3 months between the groups: pigmentation, P = 0.0002; vascularity, P = 0.0002; and height, P < 0.0001. CONCLUSIONS: The silicone gel sheet has a favorable aesthetical effect for normally created surgical scars in the Asians. Its application can reduce the conspicuousness of scars more rapidly than without.

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.

A three-dimensional analysis of the relationship among lower facial width, bony width, and masseter muscle volume in subjects with prominent mandible angles.

Despite the fact that a face with a square appearance is determined by surface anatomic features, skin surface parameters and their relationship with inner anatomic features have not been evaluated owing to the challenge of accurately and consistently measuring skin landmarks.We introduce 2 surface distances of the lower face obtained from images of skin and bone thresholds from three-dimensional computed tomographic scans; these were realigned in identical positions using the Frankfurt horizontal plane. The selected parameters were skin surface (LFOP) and bony width (MOP) of the occlusal plane level, skin surface (LFBP) and bony width (MBP) of the bigonial plane level, masseter volume (MV), and soft tissue thickness. Ten subjects with mandible angle flaring and 10 control subjects without flaring were evaluated.The parameters LFOP, LFBP, MBP, and MV showed differences between the study and control groups (P < 0.05). Lower facial width of the occlusal plane was longer than LFBP in both groups (P < 0.005), and MOP was shorter than MBP in the study group (P < 0.005), whereas MOP was greater than MBP in the control group (P < 0.001). Correlation analysis revealed that skin surface width was significantly related to bony width only in the control group (r > 0.6). Masseter volume showed no significant relationship with any skin surface or bony parameter but with soft tissue thickness in the control group (r > 0.6).In conclusion, skin surface widths (LFOP and LFBP) along with MV and bony width differ between patients with flared and nonflared mandibles. Our findings suggest that the skin surface width of the lower face can be used as a valuable landmark.

Transport disc distraction osteogenesis for the reconstruction of a calvarial defect.

PURPOSE: Reconstruction of bone defects is possible through distraction osteogenesis using small bone transport discs. The aim of this study was to evaluate the usability of transport disc distraction osteogenesis (TDDO) in the reconstruction of skull defects in an animal experiment. METHODS: Eleven mongrel female dogs were used. Craniectomy (33 x 15 mm) was performed on both sides of the parietal bone symmetrically. On the experimental site, the 7 x 15-mm transport bone disc was used for TDDO. The control site was left in the defect state. An external distraction device was used. The latency period was 5 days, the rate of distraction was 1 mm/d, and distraction was done for 26 days. After a 6-month consolidation period, a computed tomographic scan was performed. The area of regenerated bone was measured from the computed tomographic scan. The hardness was checked on the regenerated bone and the normal bone. A histologic examination of the regenerated bone was done. RESULT: Eight cases were included in the evaluation, and 3 cases were excluded because they showed early escape of the distraction device. The mean (SD) area of the regenerated bone was 57.1% (26.3) in the experimental site and 41.8% (21.3) in the control site, which was not a statistically significant difference (P > 0.05). The mean (SD) hardness was 0.50 (0.17) MPa in the experiment site and 0.55 (0.29) MPa in the normal calvarial bone; the difference was not statistically significant (P > 0.05). On histologic examination, membranous ossification was found in the regenerated bone in the experimental site. CONCLUSIONS: Transport disc distraction osteogenesis can induce new bone formation with hardness comparable to that of a normal bone. However, the amount of regenerated bone is not sufficient to allow TDDO to be substituted for conventional autogenous bone grafts.

Evidence that TGFA influences risk to cleft lip with/without cleft palate through unconventional genetic mechanisms.

This study examined the association between markers in transforming growth factor alpha (TGFA) and isolated, non-syndromic cleft lip with/without palate (CL/P) using a case-parent trio design, considering parent-of-origin effects. We also tested for gene-environmental interaction with common maternal exposures, and for gene-gene interaction using markers in TGFA and another recognized causal gene, IRF6. CL/P case-parent trios from four populations (76 from Maryland, 146 from Taiwan, 35 from Singapore, and 40 from Korea) were genotyped for 17 single nucleotide polymorphisms (SNPs) in TGFA. The transmission disequilibrium test was used to test individual SNPs, and the parent-of-origin likelihood ratio test (PO-LRT) was used to assess parent-of-origin effects. We also screened for possible gene-environment interaction using PBAT, and tested for gene-gene interaction using conditional logistic regression models. When all trios were combined, four SNPs showed significant excess maternal transmission, two of which gave significant PO-LRT values [rs3821261: P = 0.004 and OR(imprinting) = 4.17; and rs3771475: P = 0.027 and OR(imprinting) = 2.44]. Haplotype analysis of these two SNPS also supported excess maternal transmission. We saw intriguing but suggestive evidence of G x E interaction for several SNPs in TGFA when either individual SNPs or haplotypes of adjacent SNPs were considered. Thus, TGFA appears to influence risk of CL/P through unconventional means with an apparent parent-of-origin effect (excess maternal transmission) and possible interaction with maternal exposures.

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.

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.

Excess maternal transmission of markers in TCOF1 among cleft palate case-parent trios from three populations.

Isolated cleft palate is among the most common human birth defects. The TCOF1 gene has been suggested as a candidate gene for cleft palate based on animal models. This study tests for association between markers in TCOF1 and isolated, nonsyndromic cleft palate using a case-parent trio design considering parent-of-origin effects. Case-parent trios from three populations (comprising a total of 81 case-parent trios) were genotyped for single nucleotide polymorphisms (SNPs) in the TCOF1 gene. We used the transmission disequilibrium test and the transmission asymmetry test on individual SNPs. When all trios were combined, the odds ratio for transmission of the minor allele, OR(transmission), was significant for SNP rs15251 (OR = 2.88, P = 0.007), as well as rs2255796 and rs2569062 (OR = 2.08, P = 0.03; OR = 2.43, P = 0.041; respectively) when parent of origin was not considered. The transmission asymmetry test also revealed one SNP (rs15251) showing excess maternal transmission significant at the P = 0.005 level (OR = 6.50). Parent-of-origin effects were assessed using the parent-of-origin likelihood ratio test on both SNPs and haplotypes. While the parent-of-origin likelihood ratio test was only marginally significant for this SNP (P = 0.136), analysis of haplotypes of rs2255796 and rs15251 suggested excess maternal transmission. Therefore, these data suggest TCOF1 may influence risk of cleft palate through a parent-of-origin effect.

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.

Parent-controlled analgesia in children undergoing cleft palate repair.

The aims of this study were to find an optimal basal infusion dose of fentanyl for parent-controlled analgesia (PrCA) in children undergoing cleft palate repair and the degree of parents' satisfaction with PrCA. Thirty consecutive children between 6 months and 2 yr of age were enrolled. At the end of surgery, a PrCA device with a basal infusion rate of 2 mL/hr and bolus of 0.5 mL with lockout time of 15 min was applied. Parents were educated in patient-controlled analgesia (PCA) devices, the Wong Baker face pain scoring system, and monitoring of adverse effects of fentanyl. Fentanyl was infused 0.3 microgram/kg/hr at first, and we obtained a predetermined fentanyl regimen by the response of the previous patient to a larger or smaller dose of fentanyl (0.1 microgram/kg/hr as the step size), using an up-and-down method. ED50 and ED95 by probit analysis were 0.63 microgram/kg/hr (95% confidence limits, 0.55-0.73 microgram/kg/hr) and 0.83 microgram/kg/hr (95% confidence limits, 0.73-1.47 microgram/kg/hr), respectively. Eighty seven percent of the parents were satisfied with participating in the PrCA modality. PrCA using fentanyl with a basal infusion rate of 0.63 microgram/kg/hr can be applied effectively for postoperative pain management in children undergoing cleft palate repair with a high level of parents' satisfaction.

Cranial growth after distraction osteogenesis of the craniosynostosis.

The authors describe the continuance of the growth of the distracted cranium after the reshaping of the cranium by distraction osteogenesis (DO) in children with simple symmetric and asymmetric craniosynostosis. From 2000 until 2002, 9 children with simple craniosynostosis underwent cranial reshaping by gradual distraction using an external distraction device. Four patients have symmetric deformities caused by bicoronal and sagittal craniosynostosis, and 5 patients have asymmetric deformities caused by unicoronal and unilambdoidal craniosynostosis. The distraction device was developed and applied by the author. Preoperative simulation surgery was done on the three-dimensional rapid prototyped model and on the three-dimensional computerized tomography scan to determine the favorable osteotomy line. The distraction rate was from 1 to 1.5 mm/d, and the latency period was from 1 to 5 days. The extent of distraction was determined on the basis of the results of simulation surgery and the change of external appearance. Evaluation of the growth of reshaped cranium was processed from the data of the reconstructed three-dimensional computerized tomography scans before operation, immediate end of distraction, and the last follow-up time. The anteroposterior length and bitemporal width were measured in symmetric synostosis cases, and the distance from supratrochlear notch to occiput was measured in asymmetric synostosis cases. The results showed that the immediate morphologic changes of cranium after DO were maintained in both symmetric and asymmetric synostosis up to the last follow-up without evidence of relapse. Cases of asymmetric deformity also showed that the affected side and the unaffected side had grown with the maintenance of the symmetry that was corrected at the immediate end of the distraction. The cranium modified by the DO was well maintained with the children's growth without any signs of recurrent restricted growth of the original disease. The corrected symmetry of asymmetric deformity was well maintained during a long-term follow-up period as well.

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 II/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 microg/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.

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=9x10(-6) and P=5x10(-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.

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.