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In the recent past, we have observed a possible role of 10398A and 16189C mtDNA and PGC1α p.Thr394Thr (rs2970847) and p.Gly482Ser (rs8192673) variant genotypes providing susceptibility/protection against type 2 diabetes mellitus (T2DM) in two North Indian population groups. These initial observations encouraged us to look at the candidate genes in combination with –866G/A (rs659366) polymorphism in uncoupling protein 2 (UCP2) in a single study of a relatively large sample size, constituted of both the cohorts, to unravel an interesting outcome of an additive interaction in-between the studied genes. In a total of 1,686 individuals (762 cases and 924 controls) belonging to Indo-European linguistic group from North India, a comparison of risk genotype combinations of: UCP2–866GG, mtDNA 10398A and PGC1α p.Thr394Thr or p.Gly482Ser against the protective genotypes: UCP2–866XA, mtDNA 10398G and PGC1α p.Thr394Thr (nominal P value = 1.75 × 10−14, Odds ratio, OR = 5.29, 3.40–8.22 at 95% CI) or PGC1α p.Gly482Ser (nominal p value = 4.42 × 10−24, OR = 8.59, 5.53–13.35 at 95% CI), showed a highly significant difference and increased ORs. In a complex disease, it is always encouraging to find an additive interaction of multiple small effects of the studied candidate gene variations. An erratum to this article is available at .  相似文献   

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The interleukin (IL)-1β-511 C/T polymorphism has been shown to be functional and to contribute to the risk of gastric cancer. However, the relationship between the IL-1β-511 C/T polymorphism and gastric carcinogenesis remains inconclusive. A systematical electronic search was conducted of the MEDLINE, EMBASE, and CENTRAL databases. A random and a fixed effects model were exploited to estimate summary odds ratios and 95 % confidence intervals. Subgroup and sensitivity analyses were carried out with respect to ethnicity, quality assessment scores, control sources, genotyping methods, cancer histopathology and location, and Helicobacter pylori (H. pylori) infection. A total of 45 studies containing 9,066 cases of gastric cancer and 11,192 control subjects satisfied the inclusion criteria. The IL-1β-511 C/T polymorphism was found to enhance the risk of stomach cancer for overall and HWE-satisfying studies. Asians showed a positive relationship in both the overall and HWE-satisfying groups, whereas Caucasians did not. Based on subgroup analysis, H. pylori infection and genotype analysis using PCR–RFLP methods increase the association between IL-1β-511 T allele carrier and risk of stomach cancer. A positive relationship was found between the IL-1β-511 C/T SNP and stomach carcinoma susceptibility, and the results suggest that Asian ethnicity, H. pylori infection and methodologically, PCR–RFLP genotyping strengthen this relationship. Reflecting on prevalence of H. pylori in Asian countries, additional studies on the IL-1β-511 C/T SNP in the context of ethnicity and H. pylori infection may provide key insights into the mechanism underlying gastric cancer carcinogenesis. It was found PCR–RFLP is the most reliable genotyping method, and thus, it is recommendable to adopt it to determine the presence of the IL-1β-511 C/T SNP.  相似文献   

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