Adiponectin, a product of the adiponectin (ADIPOQ) gene, is the most abundant human adipose-specific protein [5]. It belongs to a family of adipocytokines, including adiponectin, leptin, resistin, and visfatin [6]. Adipocytokines are soluble mediators derived mainly from adipocytes and are thought to play an important role in inflammation and immunity [7]. Different adiponectin levels were found to be related to risks of type 2 diabetes, atherosclerosis, and coronary artery disease, among others [8, 9]. Similarly, plasma, urine, and renal levels and expression of adiponectin were found to be associated with insulin resistance, body mass index, c-reactive protein, and nephritis in patients with SLE [10, 11]. Although adiponectin has been suggested as a biomarker for SLE and SLE nephritis, other potential factors may prompt its elevation in SLE [12]. Thus, adiponectin has not been validated as a true SLE biomarker.

A group of researchers recently found that plasma adiponectin levels are significantly lower in obesity, type 2 diabetes, hypertension, atherosclerosis, and other diseases [13], while in SLE, diabetic nephropathy, and chronic renal failure, the plasma and urine levels of adiponectin are significantly raised [11, 14]. These phenomena exist for a number of reasons. First, insulin resistance in obesity, type 2 diabetes, hypertension, atherosclerosis, and other diseases is a process of attaining a state of energy equilibrium. Low serum adiponectin levels can be viewed as a pathophysiological process in the initial event of insulin resistance. The negative energy balance of insulin resistance in SLE can stimulate the secretion of adiponectin to overcome the inhibiting factor, and serum adiponectin levels increase significantly. Second, proteinuria in SLE patients causes simultaneous loss of large amounts of plasma albumin, certain immunoglobulin, complement components, and metal-binding proteins. This loss may cause degradation of the adiponectin enzymes and clear adiponectin disorder. Third, as a protective cytokine, adiponectin may reduce the metabolic disorder and endothelial vascular injury caused by other risk factors in SLE patients. It stimulates secretion of adiponectin to overcome the inhibiting factor, so that serum adiponectin level is significantly raised.

Adiponectin is an adipocyte-derived peptide expressed exclusively in adipocytes. Adiponectines are also called gelatin-binding protein-28 (GBP28), AdipoQ, ACRP30, or apM1. Low plasma adiponectin concentration is associated with metabolic disorders and an increased risk of cardiovascular events [23]. However, circulating adiponectin levels have been reported to be significantly increased in patients with SLE, while patients with high plasma adiponectin had poor prognosis in lupus nephritis [10, 24]. Serum levels of adiponectin were significantly and inversely correlated with insulin resistance in SLE patients. Elevated levels of adiponectin in SLE suggest the possible involvement of adiponectin in insulin resistance and alteration of insulin sensitivity [25].

Some studies showed that the plasma level, expression, and biological effects of adiponectin are associated with polymorphism in the ADIPOQ gene [26–28]. Polymorphisms in the ADIPOQ gene have also been shown to correlate with adiponectin serum levels, in which the expression of the G allele at SNP rs2241766 was consistently higher than the T allele among all study subjects [28]. Moreover, Hara et al. reported that the C allele at SNP rs1501299 is inversely associated with lower plasma adiponectin concentration in Japanese population. Yang and Chuang reported that the A allele at SNP rs1501299 is associated with lower serum adiponectin concentration in Italians [23, 27]. There are other factors that have been shown to regulate adiponectin levels. A Mediterranean diet or a diet rich in whole grain and fat was shown to produce increased adiponectin levels [29, 30]. Physical activity was also shown to influence adiponectin, and high levels of physical activity could elevate adiponectin levels [31].

Based on these studies, we started this study with the hypothesis that the ADIPOQ gene polymorphisms may be one of the genetic factors that affect SLE susceptibility. However, our results show that the SNP rs2241766 and rs1501299 in the ADIPOQ gene had no association with SLE in the Chinese Han population. No significant difference was found in allele or genotype frequencies between SLE patients and the controls in terms of the selected SNPs. This finding is contrary with our hypothesis and suggests that this polymorphism should be tested in groups of different ethnic origins.

Although deciphering the reasons for failure and finding a positive association is difficult, several possibilities should necessarily be considered. First, SLE is a multifactorial disease; different individuals could be exposed to various environmental factors and genetic susceptibility might lead to different results. Second, the disparity between our results and assumptions may be due to the relatively small number of SLE patients tested. A variation in ADIPOQ gene may contribute to susceptibility to SLE, but the effect should be minimal. Large, varied populations of SLE patients should be tested to avoid a statistical false negative. Third, although the investigated SNPs (rs2241766 and rs1501299) do not affect susceptibility to SLE in our study, further research on more SNPs in the ADIPOQ gene is needed to exclude the role of the adiponectin gene polymorphisms as a possible susceptibility factor for SLE. Finally, the inadequate study design, such as nonrandom sampling, should also be considered. The possibility of selection bias from the hospital-based case-control study is a relevant issue. Nevertheless, the results of this study provide additional information and motivation for further research into the association of ADIPOQ gene polymorphisms and SLE.