Applicability of Allele/genotype Frequency from Documented Controls for Case-Control Studies on Genotypes among Japanese: MTHFR C677T as an Example

In a case-control study, controls have to be selected from the population where cases are identified. However,there is an idea to make common controls applicable for different case-control studies, which could reducestudy costs. This study compared methylenetetrahydrofolate reductase C677T among subjects from differentstudies, to examine the applicability of combined subjects as controls. Case-control studies and cross-sectionalstudies with more than 100 Japanese controls or subjects were selected from PubMed in December 2008. Between1996 and 2008, 31 eligible studies with 14,510 subjects in total were published; the 677T allele frequency variedfrom 0.300 to 0.438. The genotype frequencies were all in Hardy-Weinberg equilibrium. The average weightedwith the number of subjects was 0.385. The 95% confidence interval (95%CI) of 10 studies did not include theweighted average. The study whose proximal limit of 95%CI was furthest from the weighted average was removed,and then the weighted average was recalculated. Through the process, 7 studies were excluded, resulting in theremaining 24 studies having a 95%CI including the weighted average (0.391) with 10,854 subjects. Of the 7excuded studies, one was from patients enrolled in a clinical study (0.431), two were relatively isolated (0.300and 0.438), two were published ten years ago (0.315 and 0.334), one was from a study whose allele frequency offemale subjects was 0.382 (0.436), and one had a large sample size (0.360). This example demonstrated that theallele frequency of MTHFR 677T was in common among 24 out of 31 Japanese studies, suggesting that thecalculated allele frequency could be used for Japanese case-control studies, whose cases are sampled in a generalpopulation.