Variation in the IGF-1 gene is associated with lymphocyte subset counts in neonates: The Generation R Study
Objective: IGF-1 stimulates growth, development and function of lymphocytes. The aim of this study was to examine whether functional variants of the IGF-1 gene are associated with absolute lymphocyte subset counts in neonates. Study design and measurements: This study was embedded in the Generation R Study, a prospective cohort study from foetal life onwards. A polymorphism in the IGF-1 promoter region was genotyped in cord blood DNA. Lymphocytes (T, B and NK) and T lymphocyte subsets (helper, cytotoxic, naïve and memory) in cord blood were immunophenotyped in 380 neonates by six-colour flow cytometry. Results: In total, 39% of the neonates were homozygous for the 192-bp allele (wild-type), 48% were heterozygous and 13% were noncarrier. No differences in absolute lymphocyte and T lymphocyte subset counts were observed between the 192-bp allele heterozygous and homozygous groups. In noncarriers, we found 15% lower T lymphocyte (P = 0.03), 22% lower B lymphocyte (P = 0.04) and 10% lower NK lymphocyte counts (P = 0.36) than in the 192-bp allele homozygous group. Analyses of T lymphocyte subsets showed 16% lower helper T lymphocyte counts (P = 0.01) in noncarriers. No significant differences were found for cytotoxic, naïve and memory T lymphocyte counts. All associations were adjusted for gravidity, mode of delivery, gestational age, birth weight, gender and 1- and 5- min Apgar scores. Conclusions: Our study showed associations between this IGF-1 promoter region polymorphism and absolute lymphocyte subset counts in neonates. These results should be regarded as hypothesis generating until they have been replicated in other studies.