Influence of and polymorphisms on spontaneous preterm birth in North East Brazil: genetics and preterm birth.

The mannose-binding lectin () and nitric oxide synthase 3 () genes are associated with the immune response against inflammatory processes, have been reported as possibly related with premature birth. Until now, most of the researches regarding the genetic influence of prematurity have revealed limited results because only investigating the child or the mothers' genotypes, thus not exploring the possible effects of interactions between these genotypes or the interactions with environmental factors related to the duration of pregnancy. We performed a replica study investigating the influence of single nucleotide polymorphisms (SNPs) in and genes on premature birth, also considering socioeconomic, demographic, and gestational factors. We conducted a case-control study with 189 mother-infant dyads, with 104 spontaneous preterm births and 85 term births from Recife, Brazil. We used peripheral blood samples and umbilical cord samples to extract DNA. Functional SNPs at exon 1 and promoter region of 2 and RS1799983 SNP were genotyped using direct sequencing and fluorescent allelic specific TaqMan assays respectively. Data were analyzed using the (SPSS) program with bivariate association and logistic multivariate regression tests. We observed a prevalence of wild-type genotype in the mother-infant dyad of the preterm group and polymorphic genotype in the mother-infant dyad of term birth. The haplotype LYA predominated in our sample, being more frequent in the preterm group, while the haplotype LYB, correlated with lower levels of MBL protein, was more frequent in the term birth group. About RS1799983 SNP, the G/G genotype was more frequent throughout the sample. The heterozygous genotype predominated among women from the preterm group, showed a borderline difference between the groups. When genotypes of the mother and son were analyzed together, codon 54 of remained associated with prematurity. When the variables with value lower than .20 in the bivariate analysis were analyzed by logistic regression, the low weight of the pregnant woman in relation to the gestational age, the occurrence of preterm premature rupture of membranes, urinary tract infection during birth and maternal history of other premature births were risk factors to prematurity. On the other hand, the presence of B allele at codon 54 of maternal was a protective factor for the occurrence of spontaneous premature birth. In contrast, a borderline association was established between the maternal genetic variation within gene and the outcome studied. Our study, limited by the small number of patients enrolled, indicates that and functional SNPs are associated with the occurrence of spontaneous prematurity and the regulation of the maternal inflammatory response. Despite these results are in agreement with previously reports, our findings do not replicate the ones reported in a large genome-wide association study performed on quite high number of subjects. Thus, we can conclude that and functional SNPs are plausible candidate risk factors just in few preterm birth cases, and consequently they cannot be included in the general diagnostic practice.