Genome-wide meta-analysis identified novel variant associated with hallux valgus in Caucasians.

BACKGROUND: Hallux valgus, one of the most common structural foot deformities, is highly heritable. However, previous efforts to elucidate the genetic underpinnings of hallux valgus through a genome-wide association study (GWAS) conducted in 4409 Caucasians did not identify genome-wide significant associations with hallux valgus in both gender-specific and sex-combined GWAS meta-analyses. In this analysis, we add newly available data and more densely imputed genotypes to identify novel genetic variants associated with hallux valgus. METHODS: A total of 5925 individuals of European Ancestry were categorized into two groups: 'hallux valgus present' (n = 2314) or 'no deformity' (n = 3611) as determined by trained examiners or using the Manchester grading scale. Genotyping was performed using commercially available arrays followed by imputation to the Haplotype Reference Consortium (HRC) reference panel version 1.1. We conducted both sex-specific and sex-combined association analyses using logistic regression and generalized estimating equations as appropriate in each cohort. Results were then combined in a fixed-effects inverse-variance meta-analyses. Functional Mapping and Annotation web-based platform (FUMA) was used for positional mapping, gene and gene-set analyses. RESULTS: We identified a novel locus in the intronic region of CLCA2 on chromosome 1, rs55807512 (OR = 0.48, p = 2.96E-09), an expression quantitative trait locus for COL24A1, a member of the collagen gene family. CONCLUSION: In this report of the largest GWAS of hallux valgus to date, we identified a novel genome-wide significant locus for hallux valgus. Additional replication and functional follow-up will be needed to determine the functional role of this locus in hallux valgus biology.

Relationship of vitamin D receptor gene polymorphisms with susceptibility, surgical outcome and prognosis of hallux valgus in a Chinese Han population.

BACKGROUND: This study aimed to identify the relationship between the vitamin D receptor (VDR) BsmI gene polymorphism and risk factors, surgical outcome and prognosis of hallux valgus (HV). METHODS: A case-control study was performed on a cohort of 236 HV patients and 236 controls in a Chinese Han population. Detection of the VDR BsmI/G2A polymorphism was performed using restriction fragment length polymorphism-polymerase chain reaction. RESULTS: We detected a statistically significant difference in the allele distribution of the BsmI polymorphism between cases and controls (p<0.01). Significant loss of hallux valgus angle (HVA) and intermetatarsal angle (IMA) correction was only noted in patients with the bb genotype during the 2-year follow-up period (p<0.01). The average American Orthopaedic Foot and Ankle Society (AOFAS) scores at the 2-year follow-up were decreased in both groups when compared with those at the 6 month follow-up, and 1.45 points more decrease in patients with the bb genotype was observed as compared to those with the BB and Bb genotypes (p<0.0001). The average visual analogue scales (VAS) also had the tendency with more pains in the bb genotype group (p<0.0001). Furthermore, larger numbers of transfer metatarsalgia were found in patients with the bb genotype upon 2-year follow-up (p=0.049). CONCLUSIONS: We report the first candidate gene polymorphism associated with susceptibility, surgical outcome and prognosis of HV in a Chinese Han population. Moreover, development of genetically-based method to predict the surgical outcome accurately and individualized therapy for HV are warranted.

Mild-to-Moderate Hallux Valgus Does Not Decrease Ankle Muscle Strength in Middle-Aged Japanese Women: A Comparative Study.

Extreme hallux valgus has been documented to be related to lower functional ability and health-related quality of life. It also has a negative effect on foot structure and biomechanical characteristics, which in turn may affect muscle strength in the foot and ankle. Thus, the purposes of this study were to determine whether there is a difference of ankle muscle strength in varied hallux valgus deformities and to investigate correlations between hallux valgus angles and ankle muscle strength. Hallux valgus angles and ankle muscle strength data were collected from 31 middle-aged Japanese women. The hallux valgus angle was measured with a 3-dimensional foot scanner; ankle muscle strength was measured with a dynamometer. Results showed no differences in ankle muscle strength between normal and mild-to-moderate hallux valgus at both 60º/second and 120º/second (p > .05). Unexpectedly, women with mild-to-moderate hallux valgus had a greater value for inversion peak torque per body weight and eversion-to-inversion ratio than those with normal hallux valgus (p = .019 and p = .022) at 120º/second. Furthermore, hallux valgus was correlated with inversion peak torque and peak torque per body weight (r = 0.47; p = .012 and r = 0.50; p = .007) and associated with eversion-to-inversion strength ratio (r = -0.47; p = .012). The findings indicated that mild-to-moderate hallux valgus did not result in a decrease in ankle muscle strength. Conversely, mild-to-moderate hallux valgus had greater ankle inversion strength in middle-aged Japanese women. Further studies are needed to investigate ankle muscle strength in severe hallux valgus deformities.

Association of Vitamin D Receptor Gene TaqI, BsmI, FokI, and ApaI Polymorphisms and Susceptibility to Hallux Valgus in the Chinese Population.

Previous studies have indicated that vitamin D receptor (VDR) TaqI, BsmI, FokI and ApaI gene polymorphisms are associated with the risk of skeletal malformations with inflammation. However, the potential association of VDR gene polymorphisms with the susceptibility to hallux valgus remains unclear. To clarify this association, we compared the genotypes of 228 patients with hallux valgus with those of 200 controls using the Multiplex SNaPshot system. The χ2 test was used to compare the allele and genotype frequencies between groups, and p ≤ .05 was considered statistically significant. The frequencies of the mutant allele C in TaqI (p= .036; odds ratio [OR] 1.57; 95% confidence interval [CI] 1.03-2.39) and mutant allele A in BsmI (p= .036; OR 1.33; 95% CI 1.02-1.74) were significantly greater in the patients than in the controls. In addition, after adjusting for sex and age, TaqI (p= .047; OR 1.61; 95% CI 1.00-2.58) and BsmI (p= .025; OR 1.67; 95% CI 1.06-2.61) were associated with the risk of hallux valgus through a dominant genetic model. A homozygous genetic model of BsmI was also significantly associated with the risk of hallux valgus (p= .033; OR 1.81; 95% CI 1.05-2.57). However, neither ApaI nor FokI were associated with increased susceptibility. To the best of our knowledge, we have reported for the first time that VDR gene TaqI and BsmI polymorphisms might contribute to the increased risk of hallux valgus in Chinese population.

The progression of hallux valgus in the oriental Chinese population in Hong Kong.

BACKGROUND: Hallux valgus is the lateral deviation of the great toe at the MTPJ that has many attributing aetiologies. This study will aim to identify whether hallux valgus progresses over time in the oriental Chinese population in Hong Kong. METHODS: Patients with acquired symptomatic hallux valgus who presented to clinic between 2008 and 2013 were included. The deformities were analysed radiologically at presentation and pre-operative and angles were measured. These angles were analysed in relation to the waiting time from presentation to surgery. RESULTS: A sample of 43 cases from 38 patients (Mean age 63 years, range 48-80 years) were included. Forty-one cases had a hallux valgus angle (HVA) >24° at presentation (Mean 40.4°) and all had an intermetatarsal angle (IMA) >9°. A significant difference is seen with HVA (p=0.040, t=-2.128) at presentation and pre-op but not IMA (p=0.281, t=-1.095). The average wait for surgery was 705.7days which had shown significant correlation with progression in HVA (p=0.031). No significant difference was seen between IMA and waiting time to surgery (p=0.195). DISCUSSION: The findings suggests severe hallux valgus deformity does progress over time in Hong Kong. Shorter waiting times for surgery could be beneficial to this population. Level III, retrospective comparative series.

A radiographic analysis of the contribution of hallux valgus interphalangeus to the total valgus deformity of the hallux.

BACKGROUND: The hallux valgus interphalangeus (HVI) deformity is described as rare, but improved outcomes in hallux valgus (HV) surgery is associated with its surgical correction via an Akin osteotomy. The hypothesis of this study is that HVI is common and makes a significant contribution to the total valgus deformity of the hallux (TVDH). METHODS: 285 pre-operative foot radiographs (193 with HV, 92 non-HV), utilising standardised radiographic and measurement techniques, were analysed retrospectively. The hallux valgus angle (HVA), intermetatarsal angle (IMA), interphalangeal angle (IPA) and distal metatarsal articular angle (DMAA) were measured. The TVDH was calculated as the sum of the HVA and IPA. RESULTS: 163 (57.2%) of the study population were Caucasian, 119 (41.8%) African and 3 Indian (1.0%). 236 (82.8%) of the population was female. There was a statistically significant difference in the proportion of abnormal IPA in the Caucasian population 112 (68.7%) compared to the proportion of abnormal IPA in the African population 64 (53.8%), p=0.01. The average contribution of the IPA to the TVDH across the whole study population was a mean (SD) of 37.9% (21.2). The average contribution of IPA to TVDH was greater in feet without HV (58.0%) when compared to feet with HV (28.3%). HVI is common, particularly in Caucasians (p=0.01) and makes a significant contribution to the TVDH (p<0.01). The contribution to the TVDH is more significant in mild HV. There is an inverse relationship between the IPA and other angular measurements in the foot. CONCLUSION: HVI is a common entity. The significant contribution of the IPA to the TVDH dictates that HVI must be incorporated in management algorithms. The TVDH should replace the isolated concepts of HV and HVI. LEVEL OF EVIDENCE: Level III, retrospective cohort.

Factors associated with hallux valgus in a community-based cross-sectional study of adults with and without osteoarthritis.

OBJECTIVE: To determine whether hallux valgus (HV) was associated with potential risk factors, including foot pain in a large, biracial cohort of older men and women. METHODS: We conducted a cross-sectional analysis of cohort members of the Johnston County Osteoarthritis Project, of whom 1,502 had complete clinical and demographic data available (mean age 68 years, mean body mass index [BMI] 31.3 kg/m(2) , 68% women, and 30% African American). The presence of HV was assessed visually using a validated examination. Multivariate logistic regression models with generalized estimating equations for the total sample and for each sex and race subgroup were used to examine the effect of age, BMI, foot pain, pes planus, and knee or hip radiographic osteoarthritis (OA) on HV. RESULTS: HV was present in 64% of the total sample (69% for African American men, 70% for African American women, 54% for white men, and 65% for white women). The association between HV and foot pain was elevated but not statistically significant (adjusted odds ratio [aOR] 1.21, 95% confidence interval 0.99-1.47). Women, African Americans, older individuals, and those with pes planus or knee/hip OA had significantly higher odds of HV (aOR 1.17-1.48). Participants with higher BMI had lower odds of HV compared to those with normal BMI (aOR 0.54-0.72). Overall, patterns of associations were similar across subgroups. CONCLUSION: HV was associated with female sex, African American race, older age, pes planus, and knee/hip OA, and inversely associated with higher BMI. Early prevention and intervention approaches may be needed in high-risk groups; longitudinal studies would inform these approaches.

Racial differences in foot disorders and foot type.

OBJECTIVE: To describe racial differences in the frequency of structural foot disorders and pes planus and pes cavus foot types in a large cohort of African American and white men and women ages ≥50 years. METHODS: Of 1,695 Johnston County Osteoarthritis Project participants evaluated for foot disorders/types in 2006-2010, 4 with lower extremity amputation were excluded, leaving 1,691 available for analyses (mean age 69 years, mean body mass index [BMI] 31.5 kg/m(2) , 68% women, 31% African American). The most common foot disorders/types were identified using a validated foot examination. Each foot disorder/type was compared by race using logistic regression, controlling for age, BMI, and sex. Effect modification between race (African American versus white) and age, BMI (categorized as ≥30 kg/m(2) [obese] or <30 kg/m(2) [nonobese]), sex, and education was examined. RESULTS: Hallux valgus (64%), hammer toes (35%), overlapping toes (34%), and pes planus (23%) were common. Compared to whites, African Americans were almost 3 times more likely to have pes planus and were nearly 5 times less likely to have Tailor's bunions or pes cavus. Among the nonobese, African Americans were more likely than whites to have hallux valgus (adjusted odds ratio [OR(adj) ] 2.01, 95% confidence interval [95% CI] 1.39-2.92), hammer toes (OR(adj) 2.64, 95% CI 1.88-3.70), and overlapping toes (OR(adj) 1.53, 95% CI 1.09-2.13). CONCLUSION: Foot disorders are common among adults ages ≥50 years and differ by race. Future research is needed to determine the etiology of foot problems, especially those with racial differences, in order to inform prevention approaches.

Factors associated with hallux valgus in a population-based study of older women and men: the MOBILIZE Boston Study.

OBJECTIVE: To examine potential risk factors for hallux valgus in community-dwelling elders. METHOD: Data from 600 MOBILIZE Boston Study participants (386 women and 214 men) were analyzed. Hallux valgus was defined as >15 degrees angular deviation of the hallux with respect to the first metatarsal bone toward the lesser toes. Associations of hallux valgus with age, body mass index (BMI), race, education, pes planus, foot pain, and in women, history of high heel shoe use, were assessed using sex-specific Poisson regression with robust variance estimation for risk ratios (RR) and 95% confidence intervals (CI). RESULTS: Hallux valgus was present in 58% of women and 25% of men. Higher BMI was inversely associated with presence of hallux valgus in women (P trend=0.001), with the strongest inverse association observed in those with BMI of 30.0 or more compared to those with normal BMI (RR=0.7, 95% CI: 0.5, 0.9). Women, who usually wore high-heeled shoes during ages 20-64 years compared to those who did not, had increased likelihood of hallux valgus (RR=1.2, 95% CI: 1.0, 1.5). Among men, those with BMI between 25.0 and 29.9 had increased likelihood of hallux valgus compared to those with normal BMI (RR=1.9, 95% CI: 1.0, 3.5). Men with pes planus were more likely to have hallux valgus (RR=2.1, 95% CI: 1.3, 3.3) compared to men without pes planus. CONCLUSION: In women, hallux valgus was associated with lower BMI and high heel use during ages 20-64, while in men, associations were observed with higher BMI and pes planus. Our results suggest that the etiologic mechanisms for hallux valgus may differ between men and women.