Food insecurity and coping strategies associate with higher risk of anxiety and depression among South African households with children.

OBJECTIVE: To investigate food insecurity and related coping strategies, and their associations with the risk of anxiety and depression, among South African households with children. DESIGN: Nationally representative cross-sectional study. Tools for assessing food insecurity, coping strategies, risk of anxiety and depression were assessed from the Community Childhood Hunger Identification Project, Coping Strategies Index, Generalised Anxiety Disorder-7 and Patient Health Questionnaire-9, respectively. We used ordered logistic regression to test associations of food insecurity and coping strategies with the risk of anxiety and depression. Moderating effects of each coping strategy were tested in the associations of food insecurity with anxiety and depression. SETTING: South Africa, post COVID-19 restrictions, May-June 2022. PARTICIPANTS: 1,774 adults, weighted to 20,955,234 households. RESULTS: Food insecurity prevalence was 23·7 % among households with children. All coping strategies were used to some extent, but relying on less preferred and less expensive foods was the most used strategy (85·5 % of food-insecure households). Moving to a higher level of food insecurity was associated with >1·6 greater odds of being in a higher risk of anxiety and depression. Sending a household member to beg for food was the strongest associated factor (OR = 1·7, P < 0·001). All coping strategies partly moderated (lessened) the associations of food insecurity with a higher risk of anxiety and depression. CONCLUSIONS: Food insecurity among households with children was high following the COVID-19 pandemic. Collaborative efforts between government, private sector and civil society to eradicate food insecurity should prioritise poorer households with children, as these populations are the most vulnerable.

Exploring the national prevalence of mental health risk, multimorbidity and the associations thereof: a repeated cross-sectional panel study.

Objective and methods: South Africans were affected by the COVID-19 pandemic and resultant economic hardships. As a result, mental health within this region may have worsened. Therefore, using large scale nationally representative data, we repeated the cross-sectional panel study to investigate mental health risk post COVID-19 to explore mental health and multimorbidity and to examine the relationship between adverse childhood experiences (ACEs) and comorbid health conditions in South African adults (aged 18 years and older). Results: Post-pandemic, 26.2, 17.0, and 14.8% of the South African respondents reported being probably depressed, anxious and had suffered high exposure to early life adversity, respectively. Nationally, the prevalence of mental health across the country remained alarmingly high when compared to Panel 1. The prevalence of multimorbidity (2 or more chronic morbidities) among the South African population was reported at 13.9%, and those with 2 or more morbidities were found to have increased odds of early adversity, irrespective of differing socio-demographics. Furthermore, early adversity was also associated with multimorbidity partly via mental health. Conclusion: This repeated cross-sectional national study reiterated that the prevalence of mental health across South African adults aged 18 years and older is widespread. Mental health remains worryingly high post-pandemic where more than a quarter of respondents are probably depressed, nearly one in every five respondents are anxious, and 14.8% reported high exposure ACEs. Public health interventions need to be upscaled with efforts to reduce the incidence of early adversity that may have the ability to lower adverse health outcomes and mental ill-health in adulthood.

Socioeconomic position, perceived weight, lifestyle risk, and multimorbidity in young adults aged 18 to 35 years: a Multi-country Study.

BACKGROUND: Multimorbidity-risk is established early in life, therefore reducing modifiable risk factors such as overweight or obesity may, in part, tackle the burden of multimorbidity in later life. METHODS: We made use of a cross-sectional online survey that included young adults (18-35yrs old) from three countries - Kenya, South Africa, and the United Kingdom (n = 3000). Information pertaining to socio-demographic, health, lifestyle, and perceived weight was collected. Additionally, the sum of affirmed morbidities was used to determine a morbidity score. Likewise, a lifestyle risk score was calculated based on information obtained from questions surrounding four unhealthy lifestyle behaviours, namely current smoking, alcohol consumption, physical inactivity, and overweight/obese weight status as a confirmed clinic condition. We further explored differences in socioeconomic position, and the prevalence of perceived weight, multimorbidity, and lifestyle risk factors between the three countries. We also determined the odds ratio of multimorbidity with perceived weight as a main predictor variable. We furthermore performed a generalised structural equation model to determine whether the association between socioeconomic position and multimorbidity was mediated via perceived weight and/or lifestyle risk. RESULTS: Socioeconomic position, weight perceptions, lifestyle risk, and multimorbidity varied significantly across the different economic countries. Higher morbidity (by > 11.9%) and lifestyle risk (by > 20.7%) scores were observed in those who reported an overweight weight perception when compared to those with an underweight or normal weight perception. In pooled analyses, the odds ratio in developing 2 or more morbidities increased multiple times in those who perceived themselves as overweight (all models: OR ≥ 2.241 [95% CI ≥ 1.693; ≥ 2.966] p < 0.001), showing a larger odds ratio with high significance in those who reported 3 or more morbidities (all models: OR ≥ 3.656 [95% CI ≥ 2.528; ≥ 5.286] p < 0.001). Furthermore, this study showed that an overweight weight perception partially mediated (p ≤ 0.001) the association between socioeconomic position and multimorbidity. CONCLUSIONS: This study confirmed poorer health outcomes in those who perceived themselves as overweight. The findings from this study further emphasise the importance of targeted intervention strategies directed at raising weight-related awareness and potentiating risk factors, specifically in those who reside in lower economic developed countries.

The impact of HIV and ART exposure during pregnancy on fetal growth: a prospective study in a South African cohort.

BACKGROUND: In utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women. METHODS: This prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV. RESULTS: A trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology. CONCLUSION: Our findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only.

The Effects of COVID-19 Pandemic Lockdowns on Alcohol Consumption and Tobacco Smoking Behaviour in South Africa: A National Survey.

INTRODUCTION: During the first phase of the coronavirus (COVID-19) pandemic lockdowns in South Africa (SA), both alcohol and tobacco were considered non-essential goods and their sales were initially prohibited and further restricted to certain days and timeframes. This study investigates self-reported changes in alcohol consumption and tobacco smoking behaviour in the general population during the COVID-19 pandemic lockdowns in SA. METHODS: A cross-sectional national survey was conducted in October 2021 (before the Omicron wave 4 and while SA was in low-level lockdown) among 3,402 nationally representative respondents (weighted to 39,640,674) aged 18 years and older. Alcohol consumption and tobacco use were assessed from the beginning of the lockdown towards the end of March 2020 until October 2021 using the WHO-AUDIT and the US Centre for Disease Control (CDC) Global Adult Tobacco Survey questionnaires, respectively. RESULTS: Among those that drank alcohol (33.2%), 31.4% were classified as having a drinking problem that could be hazardous or harmful and 18.9% had severe alcohol use disorder during the COVID-19 lockdowns. Twenty-two per cent (22.0%) of those that reported alcohol consumption reported that the COVID-19 pandemic lockdowns changed their alcohol consumption habits, with 38.1% reporting a decreased intake or quitting altogether. Among the one in five respondents (19.2%) who had ever smoked, most reported smoking at the time of the survey (82.6%) with many classified as light smokers (87.8%; ≤10 cigarettes/day). Almost a third (27.2%) of those smoking reported that the COVID-19 pandemic lockdowns had changed their use of tobacco products or vaping, with 60.0% reporting a reduction/quitting tobacco use. Given that sales were restricted this indicates that people could still get hold of tobacco products. Heavy smoking was associated with older age (p = 0.02), those classified as wealthy (p < 0.001), those who started or increased tobacco smoking during the pandemic lockdowns (p = 0.01) and residential provinces (p = 0.04). CONCLUSION: Given restrictions on the sale of alcohol and tobacco in SA between 27 March and August 17, 2020, during the pandemic, respondents reported an overall decline in alcohol consumption and tobacco use which might suggest that the regulatory restrictive strategies on sales had some effect but may be inadequate, especially during times where individuals are likely to experience high-stress levels. These changes in alcohol consumption and tobacco use were different from what was reported in several European countries, possibly due to differences in the restrictions imposed in SA when compared to these European countries.

Association between socio-economic status and non-communicable disease risk in young adults from Kenya, South Africa, and the United Kingdom.

There is a pressing need for global health preventions to curb the escalating burden of non-communicable diseases (NCDs). Utilising multi-country study designs can improve our understanding of how socio-economic context shapes the aetiology of NCDs, and this has great potential to advance global health interventions. We examined the association between socio-economic status (SES) and NCD risk, and the potential confounding effects of smoking and alcohol intake in young adults (18-35-year-olds) from Kenya, South Africa (SA), and the United Kingdom (UK). Our study was a cross-sectional online survey that included 3000 respondents (n = 1000 per country, 50% women) conducted in April 2022. We utilised information on twelve NCDs to classify respondents as having "no condition", "one condition", and "multimorbidity" (having two or more conditions). A total household asset score was calculated and used as a proxy of SES, and subsequently categorised into quintiles (Q1-Q5; lowest-highest). Ordered logistic regression was used to test the associations between NCD risk and exposure variables. In the UK sample, we found that those in the second lowest SES quintile (Q2) had lower odds of developing NCDs than their lowest SES counterparts (Q1). In contrast, South African and Kenyan youth with a SES score between middle and highest quintiles (Q3-Q5) were more likely to develop NCDs than the lowest SES quintile group. In all countries, smoking and/or alcohol intake were associated with higher odds of developing NCDs, and showed some confounding effects on the SES-NCD relationships. Specifically, in Kenya, the risk of developing NCD was more than two times higher in those in the middle (Q3) SES group (OR 2.493; 95% CI 1.519-4.091; p < 0.001) compared to their lowest (Q1) SES counterparts. After adjusting for smoking and alcohol, the ORs of middle (Q3) SES group changed from 2.493 to 2.241 (1.360-3.721; p = 0.002). Overall, we found that the strength and direction of SES-NCD associations differed within and between countries. This study highlights how different SES contexts shape the risk of NCDs among young adults residing in countries at different levels of economic development.

Food insecurity and coping strategies and their association with anxiety and depression: a nationally representative South African survey.

OBJECTIVE: To investigate food insecurity and related coping strategies among South African households and their associations with anxiety and depression. DESIGN: Cross-sectional study. Food insecurity and coping strategies were assessed using a modified Community Childhood Hunger Identification Project and the Coping Strategies Index questionnaires. The Generalized Anxiety Disorder-7 and Patient Health Questionnaire-9 were used to assess anxiety and depression risk. Ordered logistic regressions were used to test associations of food insecurity and related coping strategies with anxiety and depression. SETTING: South Africa during COVID-19, October 2021. PARTICIPANTS: Nationally representative sample of 3402 adults, weighted to 39,640,674 South African households. RESULTS: About 20·4 % of South African households were food insecure, with the most affected being from the lowest socio-economic groups. Shifting from 'food secure' to 'at risk' or from 'at risk' to 'food insecure' group was associated with 1·7 times greater odds of being in a higher category of anxiety or depression (P < 0·001). All coping strategies were used to some extent in South African households, with 46·0 % relying on less preferred and less expensive foods and 20·9 % sending a household member to beg for food. These coping strategies were mostly used by food-insecure households. Although the odds of moving to a higher category of anxiety and depression were observed among all coping strategies (all P < 0·001), begging for food was associated with the highest odds (OR = 2·3). CONCLUSIONS: Food insecurity remains a major health threat in South Africa. Public measures to address mental health should consider reductions in food insecurity as part of their strategy.

The prevalence of probable depression and probable anxiety, and associations with adverse childhood experiences and socio-demographics: A national survey in South Africa.

Objective and methods: Mental health problems among adults are a growing public health concern, and middle-income countries such as South Africa are disproportionally affected. Using a large scale nationally representative weighted survey, we assessed the prevalence of probable depression, probable anxiety, and adverse childhood experiences (ACEs), and explored associations between probable depression, probable anxiety, ACEs, socio-economic status, and demographic characteristics. Results: Nationally, 25.7, 17.8, and 23.6% of respondents, respectively, reported scores of ≥10 on the Patient Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7), indicating probable depression or probable anxiety, and an ACE score of ≥4 (high exposure). Overall probable depression prevalence across South Africa varied from 14.7 to 38.8%. Both probable depression and probable anxiety were more frequently reported among adults who were: retired and older (>65 years of age), and widowed, divorced, or separated; living in metropolitan areas; and only had primary school education. In a multivariable adjusted logistic regression, the likelihood of reporting probable depression or probable anxiety was also found to increase with each standard deviation increase in the ACE score (p < 0.001), independent of other socio-demographic determinants. Conclusion: The prevalence of probable depression among respondents in South Africa varies significantly across the nine provinces. Furthermore, higher ACE score and several socio-demographic determinants were associated with a higher likelihood of probable depression and probable anxiety. Adult mental health services are urgently needed to identify groups of the population vulnerable to mental health problems for better targeting of interventions. Given the range of probable depression prevalence across the country, provincial level plans and resources should also reflect the burden of mental health problems in that province.

Social vulnerability and its association with food insecurity in the South African population: findings from a National Survey.

Social vulnerability refers to the attributes of society that make people and places susceptible to natural disasters, adverse health outcomes, and social inequalities. Using a social vulnerability index (SVI), we investigated social vulnerability prevalence and its relationship with food insecurity in South Africa (SA). In this nationally representative cross-sectional survey, we calculated SVI scores from 3402 respondents (median age, 35 (26-46) years) using an SVI developed by the United States (US) Centers for Disease Control and prevention (CDC) adapted for a South African context. We measured food insecurity using a modified Community Childhood Hunger Identification Project. Findings classified 20.6% and 20.4% of adults as socially vulnerable and food insecure, respectively. The risk of food insecurity was almost threefold higher in the social vulnerability group (OR 2.76, 95% CI 2.76-2.77, p < 0.001) compared to their counterparts. The SVI could be a useful tool to guide government and policymakers in the facilitation of social relief initiatives for those most vulnerable.

Targeted proteomics of appendicular skeletal muscle mass and handgrip strength in black South Africans: a cross-sectional study.

Although appendicular skeletal muscle mass (ASM) and handgrip strength (HGS) are key components of sarcopenia, their underlying biological mechanisms remain poorly understood. We aimed to investigate associations of circulating biomarkers with ASM and HGS in middle-aged black South Africans. This study consisted of 934 black South Africans (469 men and 465 women, aged 41-72 years) from the Middle-aged Soweto cohort. Linear regression models were used to examine relationships between 182 biomarkers (measured with proximity extension assay) and dual-energy X-ray absorptiometry-measured ASM and dynamometer-measured HGS. Age, height, sex, smoking, alcohol, food insecurity, physical activity, visceral adipose tissue, HIV and menopausal status were included as confounders. Regression models showing sex-interactions were stratified by sex. The Benjamini-Hochberg false discovery rate (FDR) was used to control for multiple testing, and FDR-adjusted P values were reported. In the total sample, 10 biomarkers were associated with higher ASM and 29 with lower ASM (P < 0.05). Out of these 39 biomarkers, 8 were also associated with lower HGS (P < 0.05). MMP-7 was associated with lower HGS only (P = 0.011) in the total sample. Sex-interactions (P < 0.05) were identified for 52 biomarkers for ASM, and 6 for HGS. For men, LEP, MEPE and SCF were associated with higher ASM (P < 0.001, = 0.004, = 0.006, respectively), and MEPE and SCF were also associated with higher HGS (P = 0.001, 0.012, respectively). Also in men, 37 biomarkers were associated with lower ASM (P < 0.05), with none of these being associated with lower HGS. Furthermore, DLK-1 and MYOGLOBIN were associated with higher HGS only (P = 0.004, 0.006, respectively), while GAL-9 was associated with lower HGS only (P = 0.005), among men. For women, LEP, CD163, IL6, TNF-R1 and TNF-R2 were associated with higher ASM (P < 0.001, = 0.014, = 0.027, = 0.014, = 0.048, respectively), while IGFBP-2, CTRC and RAGE were associated with lower ASM (P = 0.043, 0.001, 0.014, respectively). No biomarker was associated with HGS in women. In conclusion, most biomarkers were associated with ASM and not HGS, and the associations of biomarkers with ASM and HGS displayed sex-specificity in middle-aged black South Africans. Proteomic studies should examine ASM and HGS individually. Future research should also consider sexual dimorphism in the pathophysiology of sarcopenia for development of sex-specific treatment and diagnostic methods.

Adiposity Mediates the Association between the Dietary Inflammatory Index and Markers of Type 2 Diabetes Risk in Middle-Aged Black South African Women.

The dietary inflammatory index (DII®), a validated tool used to measure the inflammatory potential of the diet, has been associated with metabolic disorders in various settings, but not in African populations. The aim of this study was to investigate whether the DII is associated with markers of type 2 diabetes (T2D) risk, and if this association is mediated by adiposity and/or low-grade inflammation, in black South Africa women. Energy-adjusted-DII (E-DII) scores were calculated in 190 women (median age, 53 years) from the Birth-to-Twenty plus cohort using a validated food frequency questionnaire. Fasting glucose, insulin, HbA1c, and inflammatory cytokines were measured, and an oral glucose tolerance test performed. Basic anthropometry and dual-energy x-ray absorptiometry-derived body fat, including estimate of visceral adipose tissue (VAT) area, were measured. E-DII scores were associated with all markers of T2D risk, namely, fasting glucose and insulin, HbA1c, HOMA2-IR, two-hour glucose and Matsuda index (all p < 0.05). After adjusting for age, measures of adiposity, but not inflammatory cytokines, mediated the association between E-DII and markers of T2D risk (p < 0.05). Measures of central obesity had proportionally higher (range: 23.5-100%) mediation effects than total obesity (range: 10-60%). The E-DII is associated with T2D risk through obesity, in particular central obesity, among black middle-aged South African women.

Alterations in the metabolism of phospholipids, bile acids and branched-chain amino acids predicts development of type 2 diabetes in black South African women: a prospective cohort study.

BACKGROUND: South Africa (SA) has the highest global projected increase in diabetes risk. Factors typically associated with insulin resistance and type 2 diabetes risk in Caucasians are not significant correlates in black African populations. Therefore, we aimed to identify circulating metabolite patterns that predict type 2 diabetes development in this high-risk, yet understudied SA population. METHODS: We conducted a prospective cohort study in black SA women with normal glucose tolerance (NGT). Participants were followed for 13 years and developed (i) type 2 diabetes (n = 20, NGT-T2D), (ii) impaired glucose tolerance (IGT) (n = 27, NGT-IGT), or (iii) remained NGT (n = 28, NGT-NGT). Mass-spectrometry based metabolomics and multivariate analyses were used to elucidate metabolite patterns at baseline and at follow-up that were associated with type 2 diabetes development. RESULTS: Metabolites of phospholipid, bile acid and branched-chain amino acid (BCAA) metabolism, differed significantly between the NGT-T2D and NGT-NGT groups. At baseline: the NGT-T2D group had i) a higher lysophosphatidylcholine:lysophosphatidylethanolamine ratio containing linoleic acid (LPC(C18:2):LPE(C18:2)), ii) lower proliferation-related bile acids (ursodeoxycholic- and chenodeoxycholic acid), iii) higher levels of leucine and its catabolic intermediates (ketoleucine and C5-carnitine), compared to the NGT-NGT group. At follow-up: the NGT-T2D group had i) lower LPC(C18:2) levels, ii) higher apoptosis-related bile acids (deoxycholic- and glycodeoxycholic acid), and iii) higher levels of all BCAAs and their catabolic intermediates. CONCLUSIONS: Changes in lysophospholipid metabolism and the bile acid pool occur during the development of type 2 diabetes in black South African women. Further, impaired leucine catabolism precedes valine and isoleucine catabolism in the development of type 2 diabetes. These metabolite patterns can be useful to identify and monitor type 2 diabetes risk >10 years prior to disease onset and provide insight into the pathophysiology of type 2 diabetes in this high risk, but under-studied population.

Fat redistribution and accumulation of visceral adipose tissue predicts type 2 diabetes risk in middle-aged black South African women: a 13-year longitudinal study.

BACKGROUND: Cross-sectional studies in South Africa (SA) have shown that black SA women, despite being more insulin resistant, have less visceral adipose tissue (VAT) and more subcutaneous adipose tissue (SAT) than white women. This study aimed to investigate whether baseline and/or change in body fat and its distribution predict type 2 diabetes (T2D) risk in middle-aged black SA women, 13 years later. METHODS: We studied 142 black SA women who are the caregivers of the Birth-to-Twenty plus cohort, and who had normal glucose tolerance (NGT) at baseline. At baseline and follow-up, fasting blood samples, basic anthropometry and dual-energy X-ray absorptiometry-derived body composition were measured. At follow-up, an oral glucose tolerance test was completed. The WHO diabetes diagnostic criteria were used to define NGT, impaired fasting glucose (IFG)/impaired glucose tolerance (IGT), impaired glucose metabolism (IGM) and T2D. RESULTS: At follow-up, 64% of participants remained NGT, whereas 25% developed IGM, and 11% developed T2D. The IGM and the T2D groups were combined for statistical analyses. At baseline, trunk fat mass (FM), VAT but not SAT (measures of central FM) were higher in the IGM/T2D group than the NGT group (p < 0.0001). In contrast, the IGM/T2D group had lower leg %FM at baseline than the NGT group (p < 0.0001). Baseline trunk FM (Odds ratio per 1 kg increase (95% confidence interval, 1.95 (1.43-2.67))), and VAT (OR per 10 cm2 increase, 1.25 (1.10-1.42)), and the change in VAT (1.12 (1.03-1.23)) were associated with greater odds of developing IGM/T2D, whereas baseline leg FM (OR per 1 kg increase, 0.55 (0.41-0.73)) were associated with reduced IGM/T2D risk at follow-up (p < 0.05). CONCLUSIONS: Relative fat redistribution, with VAT accumulation, predicted the development of IGM/T2D 13 years before its onset. Prevention of central obesity is a key factor to reduce the risk of developing T2D among middle-aged urban black SA women.

Type 2 diabetes mellitus in African women.

Compared to global estimates, Sub-Saharan Africa (SSA) has the highest projected rates of increase in type 2 diabetes (T2D) over the next 25years. This is attributed to the ageing population, increasing urbanisation and the associated lifestyle changes. Although the prevalence does not differ by gender, deaths attributable to T2D in SSA are greater in women, likely due to differences in beliefs and access to care. Women in SSA also have greater risk factor burden for T2D than men, in particular obesity, which is explained in part by sociocultural factors. The pathogenesis of diabetes differs between African and Caucasian women, with implications for risk assessment. African women are more insulin resistant than their Caucasian counterparts, despite a more 'favourable' body fat distribution. Notably, women in SSA face the dual burden of T2D and HIV/AIDS. HIV positive women in SSA are typically young and obese, with the latter being exacerbated by anti-retroviral therapy (ART). Cultural perceptions regarding weight loss and limited financial resources are the major limitations to the management of T2D. Hence prevention is vital. However, there is a paucity of studies examining the effectiveness and sustainability of interventions to reduce T2D in SSA.

Genes encoding proteoglycans are associated with the risk of anterior cruciate ligament ruptures.

BACKGROUND: Genetic variants within genes involved in fibrillogenesis have previously been implicated in anterior cruciate ligament (ACL) injury susceptibility. Proteoglycans also have important functions in fibrillogenesis and maintaining the structural integrity of ligaments. Genes encoding proteoglycans are plausible candidates to be investigated for associations with ACL injury susceptibility; polymorphisms within genes encoding the proteoglycans aggrecan (ACAN), biglycan (BGN), decorin (DCN), fibromodulin (FMOD) and lumican (LUM) were examined. METHODS: A case-control genetic association study was conducted. 227 participants with surgically diagnosed ACL ruptures (ACL group) and 234 controls without any history of ACL injury were genotyped for 10 polymorphisms in 5 proteoglycan genes. Inferred haplotypes were constructed for specific regions. RESULTS: The G allele of ACAN rs1516797 was significantly under-represented in the controls (p=0.024; OR=0.72; 95% CI 0.55 to 0.96) compared with the ACL group. For DCN rs516115, the GG genotype was significantly over-represented in female controls (p=0.015; OR=9.231; 95%CI 1.16 to 73.01) compared with the ACL group and the AA genotype was significantly under-represented in controls (p=0.013; OR=0.33; 95% CI 0.14 to 0.78) compared with the female non-contact ACL injury subgroup. Haplotype analyses implicated regions overlapping ACAN (rs2351491 C>T-rs1042631 T>C-rs1516797 T>G), BGN (rs1126499 C>T-rs1042103 G>A) and LUM-DCN (rs2268578 T>C-rs13312816 A>T-rs516115 A>G) in ACL injury susceptibility. CONCLUSIONS: These independent associations and haplotype analyses suggest that regions within ACAN, BGN, DCN and a region spanning LUM-DCN are associated with ACL injury susceptibility. Taking into account the functions of these genes, it is reasonable to propose that genetic sequence variability within the genes encoding proteoglycans may potentially modulate the ligament fibril properties.