Leptin is an important regulator of the mass of adipose tissue and of body weight; it operates by inhibiting food intake and stimulating energy expenditure. Some polymorphic genes involved in the regulation of leptin—the leptin gene (LEP A19G), the leptin receptor gene (LEPR Q223R, K109R, and K656N), and the peroxisome proliferator-activated receptor-gamma gene (PPARG P12A and C161T)—have been investigated as possible factors associated with obesity. Allelic frequencies of these polymorphisms show ethnic variation. The authors performed a meta-analysis of the available data on the association between these polymorphisms and obesity based on case-control studies. Odds ratios and 95% confidence intervals for obesity associated with leptin polymorphisms were calculated by using both fixed- and random-effects models. Results suggest no evidence of association between the genes under study and obesity. The lack of association could be due to the complex pathogenesis of obesity, which involves a number of genetic and environmental factors. Large studies including testing of multiple genes in both obese and lean subjects, with epidemiologic data on dietary habits in different ethnic groups, are necessary to better understand the role of leptin in regulating weight in human populations.

Lung cancer is the most common malignancy in the Western world, and the main risk factor is tobacco smoking. Polymorphisms in metabolic genes may modulate the risk associated with environmental factors. The glutathione S-transferase theta 1 gene (GSTT1) is a particularly attractive candidate for lung cancer susceptibility because of its involvement in the metabolism of polycyclic aromatic hydrocarbons found in tobacco smoke and of other chemicals, pesticides, and industrial solvents. The frequency of the GSTT1 null genotype is lower among Caucasians (10–20%) than among Asians (50–60%). The authors present a meta- and a pooled analysis of case-control, genotype-based studies that examined the association between GSTT1 and lung cancer (34 studies, 7,629 cases and 10,087 controls for the meta-analysis; 34 studies, 7,044 cases and 10,000 controls for the pooled analysis). No association was observed between GSTT1 deletion and lung cancer for Caucasians (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.87, 1.12); for Asians, a positive association was found (OR = 1.28, 95% CI: 1.10, 1.49). In the pooled analysis, the odds ratios were not significant for either Asians (OR = 0.97, 95% CI: 0.83, 1.13) or Caucasians (OR = 1.09, 95% CI: 0.99, 1.21). No significant interaction was observed between GSTT1 and smoking on lung cancer, whereas GSTT1 appeared to modulate occupational-related lung cancer.

The association between the cytochrome P-450 1B1 (CYP1B1) Val432Leu polymorphism and breast cancer was assessed through a meta-analysis of all published case-control studies and a pooled analysis of both published and unpublished case-control studies from the Genetic Susceptibility to Environmental Carcinogens (GSEC) database (http://www.upci.upmc.edu/research/ccps/ccontrol/g_intro.html). GSEC is a collaborative project that gathers information on studies of metabolic gene polymorphisms and cancer. Thirteen articles were included in the meta-analysis (14,331 subjects; 7,514 cases, 6,817 controls); nine data sets were included in the pooled analysis (6,842 subjects; 3,391 cases, 3,451 controls). A summary meta- or pooled estimate of the association between the CYP1B1 Val432Leu polymorphism and breast cancer could not be calculated because of statistically significant heterogeneity in the point estimates among studies. No association between the CYP1B1 Val432Leu polymorphism and breast cancer was observed in Asians (for Val/Val and Val/Leu combined, odds ratio (OR) = 1.0, 95% confidence interval (CI): 0.8, 1.2). An inverse association was observed in populations of mixed/African origin (OR = 0.8, 95% CI: 0.7, 0.9). The pooled analysis suggested a possible association in Caucasians (for Val/Val and Val/Leu combined, OR = 1.5, 95% CI: 1.1, 2.1), with effect modification across age categories. The observed effect of age on the association in Caucasians indicates that further studies are needed on the role of CYP1B1 Val432Leu in estrogen metabolism according to age, ethnicity, and menopausal status.

Methylenetetrahydrofolate reductase (MTHFR) is a gene involved in the process of DNA synthesis and methylation. The MTHFR C677T polymorphism has been associated with male infertility. A prospective study was conducted on men seeking care at the infertility clinic in Milano to determine if the MTHFR C677T polymorphism is associated with infertility, and if such an association is modified by a common deletion of one of the glutathione transferases, GSTM1. One year after enrolment, 46 subjects reported having had a child, while 59 were still childless. Subjects carrying the MTHFR C677T homozygous variant polymorphism were at increased risk of being infertile after 1-year follow-up (OR 3.7, 95% CI = 1.4–10.4); carriers of the homozygous variant MTHFR genotype and of a functional copy of GSTM1 appear to have a significantly higher risk of infertility (n=11; OR = 22.0 95% CI = 3.8–127.9) than subjects who carry the wild-type genotype for both genes. Such risk becomes non-significant when the GSTM1 deletion is also present (n=5; OR = 1.1 95% CI = 0.2–5.1). A possible explanation of this unexpected result could lie in the known involvement of glutathione transferases in the metabolic pathways of both methylation and transulfuration. The interaction found deserves confirmation and replication in a larger population, since it may be relevant to several chronic diseases such as cardiovascular diseases and cancer.

Many food and feed additives result from fermentation of genetically modified (GM) microorganisms. For vitamin B2 (riboflavin), GM Bacillus subtilis production strains have been developed and are often used. The presence of neither the GM strain nor its recombinant DNA is allowed for fermentation products placed on the EU market as food or feed additive. A vitamin B2 product (80% feed grade) imported from China was analysed. Viable B. subtilis cells were identified and DNAs of two bacterial isolates (LHL and LGL) were subjected to three whole genome sequencing (WGS) runs with different devices (MiSeq, 454 or HiSeq system). WGS data revealed the integration of a chloramphenicol resistance gene, the deletion of the endogenous riboflavin (rib) operon and presence of four putative plasmids harbouring rib operons. Event- and construct-specific real-time PCR methods for detection of the GM strain and its putative plasmids in food and feed products have been developed.