The complex polygenic diseases such as diabetes could be complicated by phenomena such as variable age at onset disease, or environmental triggers . Although, some phenotypes such as BMI and insulin resistance have been affected largely by genetic factors, others such as abdominal obesity have been affected largely by non-genetic factors, probably environmental [22, 23]. So, assessment characteristics of well defined phenotypic abnormalities could show clearly the association between genome and environment. On the other word by assessment the association between apo E gene polymorphism and anthropometric measures as risk factors of diabetes, it is possible to determine the association between apo E gene polymorphism and diabetes.
The role of apo E gene polymorphism in anthropometric measures has been studied in different populations. Although this study is conducted in a small sample size, this is the first study on association between apo E gene polymorphism and anthropometric measures in Iranian population. In this study Apo E3 was the most common allele in our population, and E2 followed by E4 allele have been found less frequent both in diabetics and nondiabetics. These findings are in agreement with previous reports [10, 24]. So, the frequency of apo E polymorphism could be reasonable different according to environmental factors and lifestyle behaviors, obesity, gender, population related differences (such as geographical differences), presence of CHD, and even undertreatment lipid lowering drugs [25–31].
In subgroup of patients with abnormal WC in our study, all components of anthropometric measures were higher than subgroup that had normal WC. Previous evidence also supports our finding [32–34] which may be related to insulin resistance. Our study was shown a significant difference in distribution of apo E allele frequency in patients stratified according to WC only in diabetic group. Also, there was a significant influence for apo E4 allele on central obesity. But this effect was nonsignificant for apo E2 allele. Oh et al.  found a significant correlation between WC and apo E4 allele in women with a family history of diabetes which was independent of hyperlipidemia. This suggests that mechanisms other than lipid pathways might be involved in apo E action . As the weight control is important for improving insulin sensitivity and reducing CVD risk, therefore it might be speculated that in apo E4 carriers weight control play crucial role in control of hyperglycemia and reducing CVD risk.
In our study, apo E2 allele was significantly associated with hypercholesterolemia both in women and in patients aged > 50 which was independent of diabetes. Also, lipid levels did not significantly differ between subjects with apo E3/E3 and apo E4/E3. This is in agreement with our previous results and also results by Pedro-Botet et al. who found significantly higher level of total cholesterol in patients with E2 isoform [24, 29]. In contrast, Oh et al.  found that in men with family history of diabetes, apo E2 and also apo E4 carriers had higher level of total and LDL cholesterol compared to those with apo E3/E3, although the difference was not significant. In addition, they have found that in both sexes with no family history of diabetes, apo E2 was associated with normal levels of total and LDL cholesterol . It seems the effect of apo E polymorphism on lipid metabolism may vary according to genetic background. However, the apo E polymorphism especially apo E4 seems to be a risk factor for CHD development independent of association with high level of total and LDL cholesterol [35–39].
An association between apo E2 allele and hypertriglyceridemia has been consistently reported in healthy populations [40–43]. Dallongeville et al. in their meta-analyzes have shown that triglyceride concentration is significantly higher in carrier of E2 or E4 allele than in carriers of E3 allele, at least among men and also the presence of E2 allele was related to lower and the E4 allele to higher level of total and LDL cholesterol in plasma relative to those with the E3 allele . Although our abnormal WC subgroup of T2DM patients had higher triglycerides level than the diabetics with normal WC, there were no significant correlation between apo E gene polymorphism and triglycerides level in multivariate regression. This finding is in agreement with most studies that have been done in European diabetic patients [10, 44, 45], but it is in contrast to studies on diabetic patients among Asian populations [46–48] which higher level of triglycerides in carriers of E2 allele have been reported.
In our study, the probability of being obese (BMI ≥ 30) was increased significantly in women, which was independent of apo E polymorphism or diabetes. This parameter is known to influence lipid metabolism or insulin resistance and may interfere with genetic factors. The influence of lifestyle on apo E polymorphism was clearly shown in two parts of Belgium . Although apo E has long been known as athero-protective and in excess of circulating lipids apo E would be expressed as a key peripheral contributor to the development of obesity and related metabolic dysfunctions. There are some reports in contrast to our finding. Data from the Atherosclerosis Risk in Communities (ARIC) study, showed that apo E genotypes were associated with BMI in the order of apo E4 < apo E3 < apo E2 . Another epidemiological study showed that, in older women with a family history of diabetes, apo E4 /E 4 and apoE3/E4 genotypes were correlated with increased waist circumference and obesity .
In this study, we observed that there were sex-specific effects on anthropometric measures. For example, abnormal WC was more prevalent in females both in diabetics and nondiabetics. Also, our data has shown that the probability of having obesity, central obesity, and hypercholesterolemia are increased significantly in diabetic women independent of apo E polymorphism. The sex-specific distribution of apo E gene was not differing significantly between two groups. This might be as a result of deviation in female/male ratio in our population. However, gender related differences are difficult to determine due to variations of hormonal status during pre- and post menopause in women and their effects on plasma lipid profile .
In our patients the probability of having central obesity, hypertension and hypercholesterolemia was increased significantly in diabetics according to age (≥ 50 years). When we assessed the effect of apo E2 allele on hypercholesterolemia, this trend was equal 0.36 which by considering the effect of age, this figure was changed to 2.05. The trend for increasing central obesity in E4 allele carriers was 0.22 without considering the effect of age and changed to 3.08 in presence of age > 50 years. These results showed the influence of apo E polymorphism on abdominal obesity and hypercholesterolemia was significantly changed in presence age > 50 years. One study was evaluated this effect on postprandial triglycerides . They found a significant interaction between age and apo E on postprandial triglycerides. In their study was unmasked the unfavorable effect of E2 and E4 alleles on under curve concentration by aging.
As it is expected, we found a significant increase in blood pressure just at the presence of diabetes and aging. A positive correlation between total serum cholesterol level and blood pressure  had been shown in population-based studies; which might imply the effect of apo E genotype . However, we didn’t find any significant association between apo E genotype and hypertension in our study which could be also due to the variation in sex distribution.
In this study, there was no information about diet of our patients therefore we don’t have any precise explanation for these differences. Because our study was carried out in a small population, therefore the effects observed might not be subject to generalization. The possible contribution of such association to the observed relationship between apo E4 and abdominal obesity also remains to be clarified by prospective studies.