822: Genetic susceptibility to preterm birth in the Filipino population in Hawaii

Abstract

822 Genetic susceptibility to preterm birth in the Filipino population in Hawaii Frederico Rocha, Thomas Slavin, Dongmei Li, Sandra Yamamoto, Gillian Bryant-Greenwood John A. Burns School of Medicine University of Hawaii, Department of Obstetrics, Gynecology and Women’s Health, Honolulu, HI, John A. Burns School of Medicine University of Hawaii, Department of Pediatrics, Honolulu, HI, John A. Burns School of Medicine University of Hawaii, Department of Public Health Sciences, Honolulu, HI OBJECTIVE: Filipinos have the highest preterm birth rate in the State of Hawaii. Relaxin (RLN) is a systemic hormone (sRLN) produced by the corpus luteum but is also produced by the decidua (dRLN) as a local hormone. Elevated maternal sRLN has been associated with increased risk of preterm labor (PTL) and elevated dRLN associated with preterm premature rupture of membranes (PPROM). We have sought associations of two SNPs in the RLN H2 gene promoter in Filipino patients with PTL or PPROM, as well as with their expression of cytoplasmic dRLN protein. STUDY DESIGN: Filipino patients (n 60) who delivered at 34-36 weeks gestation were subdivided into PTL (n 20) and PPROM (n 20) and compared to controls who delivered at term (n 20). Maternal DNA was used for identification by specific Taqman RT-PCR of SNPs: rs 472076 and rs 3758239. Formalin fixed sections of parietal decidua from the same patients were immunostained with a Mab to RLN H2 (Abcam) and the ImmPRESS kit (Vector Labs). All slides were blinded for multispectral imaging (Nuance) and quantitated by the Inform software. Results were expressed as mean SD and significance set at p 0.05. Kruskal-Wallis nonparametric ANOVA was used to compare differences in SNP expression and multiple comparisons were determined by the Bonferroni-Dunn’s test. RESULTS: SNP rs4742076 was significantly (p 0.0012) associated with PPROM compared to controls. The PPROM patients also had significantly more (p 0.001) dRLN expressed compared to controls. SNP rs375839 was significantly associated (p 0.0025) with both PPROM and PTL compared to the controls. However, dRLN was only significantly increased (p 0.001) in the PPROM patients. CONCLUSION: SNP rs4742076 in the RLN gene promoter and increased dRLN protein were associated with PPROM in Filipino patients in Hawaii. SNP rs3758239 was associated with both PPROM and PTL, but dRLN was only increased in the PPROM patients and not in PTL compared to the term controls. Supported by grant NIHNCRR(U54RR026136) NIHMD(U54MD007584).