The FADS insertion-deletion polymorphism drives the arachidonic acid/dihomo-gamma-linolenic acid ratio in preterm infants and may contribute to patency of ductus arteriosus - a pilot study.

BACKGROUND: The FADS Indel insertion-deletion polymorphism (rs66698963) modulates fatty acid desaturase 1 (FADS1), which converts di-homo-γ-linolenic acid (DGLA) to arachidonic acid (ARA). Adults homozygous for the I allele (I/I) have up to 84% higher ARA/DGLA ratios than D homozygotes (D/D), with heterozygotes intermediate. Whether this relationship extends to preterm neonates is unknown. ARA is the precursor to prostaglandin E2 (PGE2), a key mediator of ductal patency. Elevated ARA synthesis may contribute to patent ductus arteriosus (PDA). HYPOTHESIS: I/I infants have greater ARA/DGLA ratios, higher PDA incidence, and more catheter-based closures than D/D genotype. METHODS: We prospectively enrolled 65 premature infants (mean gestational age 28 weeks). Blood fatty acids were analyzed by gas chromatography and genotype by PCR. Genotype associations with outcomes were assessed using Fisher's exact test, Cochran-Armitage trend test, and logistic regression. Fatty acid comparisons used Welch's t-test and one-way ANOVA. RESULTS: Genotypes were D/D in 26 infants (40%), I/D in 31 (48%), and I/I in 8 (12%). The ARA/DGLA ratio was 33% higher in I/I than D/D infants (ANOVA p=0.029; Welch's t-test p=0.04) and remained significant after gestational-age adjustment (p=0.025). PDA rates increased nonsignificantly from D/D (42%) to I/D (45%) to I/I (50%) (Cochran-Armitage p=0.70; OR=1.15, p=0.70). Among 29 with echo-confirmed PDA, spontaneous closure rates were 60%, 31%, and 50%; six required Piccolo occlusion. Gestational age did not differ by genotype (p=0.68). CONCLUSIONS: The FADS Indel significantly modulates ARA/DGLA in preterm infants, consistent with adults. PDA associations were nonsignificant, but trends warrant study in larger cohorts.