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Although the birth of twins has always attracted attention, there are no known genetic or environmental factors that can determine the birth of monozygotic (MZ) twins. And even for dizygotic (DZ) twins, genetic influences are not completely understood. A previous study from our group has shown that the C allele of polymorphism rs1042522 in the TP53 gene was more frequent in the mothers of twins than in the mothers of singletons in a small village in South Brazil. In order to clarify whether this was an isolated factor, we performed a population-based, observational case-control study. Samples were selected from a state-funded program of paternity investigation. Samples were considered cases when two of the children had the same date of birth, whereas controls were those samples in which at least two children were born in different dates. The first subsequent sample fulfilling control criteria was included after each case. From 2007 to 2013, 32,661 records were searched and 283 (0.9%) twins were found (119 MZ and 164 DZ). Genotypic and allele frequencies were not different between mothers of twins or mothers of singletons. However, mothers of MZ twins showed a higher frequency of GG genotype and lower frequency of the C allele when compared to mothers of DZ twins. Also, the proportion of MZ twins (42%) was higher than usually reported (30%). Finally, the proportion of twins found in this study seems to be more realistic, as this sample was allegedly not from users of assisted reproduction techniques. [ABSTRACT FROM AUTHOR]