Haren et al. BMC Public Health 2010, 10:454 http://www.biomedcentral.com/1471-2458/10/454 Table 6 Risk of elevated GGT with obesity, metabolic syndrome and metabolic risk cluster by drinking status Non-drinkers (n = 791) Crude OR Adj. OR* Moderate drinkers (n = 552) Crude OR Adj. OR* Risky Drinkers † (n = 1183) Crude OR Adj. OR* Abdominal Obesity † Normal 1.0 Overweight 1.4 (0.6-3.5) Obese 2.0 (1.0-4.0) BMI <25 1.0 25-30 2.0 (1.1-3.8) 30+ 1.5 (0.8-2.8) Metabolic syndrome † No 1.0 Yes 2.3 (1.4-3.8) MR Cluster profile† Favorable 1.0 Adverse 1.9 (1.2-3.1) 1.0 1.5 (0.6-3.9) 2.6 (1.1-5.7) 1.0 2.0 (1.01-3.9) 1.8 (0.9-3.6) 1.0 2.4 (1.3-4.1) 1.0 1.6 (0.9-2.8) 1.0 1.5 (0.8-2.9) 1.7 (1.03-2.9) 1.0 2.1 (1.2-3.6) 1.6 (0.9- 2.8) 1.0 2.5 (1.6-3.9) 1.0 3.0 (1.9-4.8) 1.0 1.9 (0.9-3.8) 4.5 (2.3-8.6) 1.0 3.0 (1.6-5.6) 2.7 (1.4-5.2) 1.0 2.8 (1.7-4.6) 1.0 2.8 (1.6-4.9) 1.0 1.8 (1.3-2.5) 1.5 (1.2-1.9) 1.0 1.5 (1.2-2.0) 1.4 (1.0-1.8) 1.0 2.8 (2.2-3.5) 1.0 5.1 (3.9-6.6) Page 8 of 10 1.0 3.2 (2.2-4.7) 4.2 (2.9-5.9) 1.0 2.4 (1.7-3.3) 2.9 (2.1-4.1) 1.0 3.7 (2.8-5.0) 1.0 4.9 (3.7-6.7) *Adjusted by age, sex, and ethnicity, smoking, and PA level. † Risky drinking was defined as > 6 drinks on any occasion or >4 drinks per day in males and >4 drinks on any occasion or >2 drinks per day in female in the week prior to the survey. Abdominal obesity defined using WHO WC gender specific criteria: overweight being WC of 80-88 cm in females and 94-102 cm in males, while obesity being WC ≥88 cm in females and 102 cm in males. Metabolic syndrome defined by IDF criteria: waist circumference (≥94 cm in males and ≥80 for females), raised triglycerides (≥1.7 mmol/L), reduced HDL (<1.03 in males or <1.29 in females), raised blood pressure (systolic >130 mmHg or diastolic≥85 mmHg), and plasma glucose (≥5.6 mmol/L). Adverse MR (metabolic risk) cluster profile was obtained by EM cluster analysis. These findings are novel and are significant in this population. Although there are well known interactions between BMI and drinking on GGT, to the authors knowledge no published data exist regarding the interac- tion between multiple co-existing metabolic risk factors or different metabolic endophenotypes and alcohol intake on liver enzymes. This is important as the inter- actions may be much more severe for people with car- dio-metabolic risk factors over and above overweight/ obesity. Moreover, we have tested the interactions with two different methods for classifying cardio-metabolic risk: (1) the IDF metabolic syndrome definition; (2) a data driven approach to defining population metabolic endophenotypes using the same variables. This depar- ture from the controversial dichotomous classification of the metabolic syndrome in capturing the population dis- tribution of multiple metabolic risk factors is a major strength of this study. A priori, we conceived that inter- nationally used clinical cut-points for metabolic syn- drome classification may not apply equally to Australian Aboriginal and Torres Strait Islander peoples as there metabolic endophenotypes are quite different (as evi- denced in this cohort by Table 1) and thus the relations between cardio-metabolic risk factors may vary. We indeed demonstrated that there was a discrepancy (n = 524 cases) between clinical metabolic syndrome classifi- cation and metabolic endophenotypes (clusters) that dif- fered by ethnicity. Aboriginals were more likely to be classified as not having metabolic syndrome but being in the adverse MR cluster compared with Torres Strait Islanders who were more likely to be classified as metabolic syndrome but be in the favourable MR clus- ter. This could be partially due to inappropriate waist circumference cut-offs causing misclassification of IDF metabolic syndrome which may in turn partly explain the lack of interaction of alcohol drinking with meta- bolic syndrome and obesity on elevated GGT. MR clus- ters differed in their ethnic distribution, and cluster membership was mostly explained by blood pressure rather than abdominal obesity, which tends to explain clustering in Caucasian populations. These different metabolic (endo)phenotypes and their risk to future health outcomes are deserving of further study. The interactions of metabolic profile or body fat with alcohol consumption on serum GGT may be dependent on gene polymorphisms in the population that affect the level of fat accumulation in liver cells, oxidative stress, cytokine production, immune response and tissue fibro- sis [30]. However, at present no genetic associations with advanced NAFLD have been confirmed [31]. This is the first study of the associations of alcohol intake and metabolic risk, their combined influence and the potentially modifying role of gender and ethnic background on elevated serum GGT in Indigenous Aus- tralians. Although we have only studied an intermediate outcome of liver function (GGT), to date very little has been published on biochemical liver dysfunction or NAFLD in Indigenous populations worldwide. The pre- valence of elevated GGT in the communities studied (overall 25.9%: males 36.1%, females 16.5%) were com- parable to those reported in the Russian study. Similarly, in an Atayal Aboriginal community in Taiwan, the