Balanced polymorphisms in Sardinia: differential fertility due to joint effect of genetic and epidemiological factors.

It has been established that resistance to malarial infection favours the heterozygotes for "malarial genes" increasing the viability of the carriers of the gene between birth and reproductive age and their relative fertility. In the previous paper the epidemiological effect of malaria on fertility was studied resulting in a higher number of children per woman where higher was the level of morbidity. However, the frequencies of heterozygotes within areas homogeneous for malarial morbidity level showed an unexpected heterogeneity, suggesting a direct investigation on the relationship between fertility. rate and heterozygote frequency, to test the hypothesis of differential fertility maintaining balanced polymorphisms. Fertility rates in Sardinia came from the 1961 population Census, and estimate of heterozygote frequencies for thalassaemia and G-6-PD deficiency in 52 Sardinian villages came from the studies of Siniscalco et al. Data concern limes and places in which malaria was endemic. To emphasize the possible effect on reproduction due to different number of .heterozygotes, both fertility rate and infecundity rate were measured for the women living in the two areas corresponding to the two tails of the distribution of the villages' heterozygote frequency. Cultural and socio-economic factors were kept stable by selecting illiterate women living in rural villages and age at marriage was considered as covariate. The results seemed to confirm the Haldane hypothesis. The average number of live born children was significantly higher in the villages with higher percentages of heterozygotes than in the low heterozygote frequency area (6.03 vs 5.06, P«0.001). The difference between percentages of women without children was in the expected opposite direction (9.46 vs 12.80, P«0.001). The joint effect of genetic and epidemiological faclors on fertility rates was studied in order to explain the incomplete overlapping of heterozygote frequency levels and morbidity levels. The mean number of live births per woman in areas where both the percentage of Th+ heterozygotes and level of malaria were low was much lower (4.60) than that for women in areas where heterozygotes and malaria were both at high levels (6.44). The same results were obtained when G-6-PD deficiency polymorphism was considered. The percentage of women without children also seems to be influenced by the combined effect of the two factors. Therefore, differential fertility seems to have maintained malarial polymorphisms. However, acquired immunity, depending on the level of endemicity in an area, may contribute to lowering or increasing the fitness which was already influenced by stable balanced polymorphisms.