Abstract

Relationship between Digit Ratio and Idiopathic Pulmonary Arterial Hypertension in Japanese Women

Tsunehisa Yamamoto, Yuichi Tamura, Tomohiko Ono, Makoto Takei, Motoaki Sano, Masaharu Kataoka, Hiroyuki Yamagishi, Toru Satoh and Keiichi Fukuda

Aim: Endothelin-1 (ET-1) is the key vasoactive mediator in patients with pulmonary arterial hypertension (PAH), and sex steroids are known to influence ET-1 levels. Additionally, the second to fourth digit (2D:4D) ratio is a biometric marker influenced by testosterone concentrations and androgen receptor sensitivity in the uterus, and some reports have linked (2D:4D) ratio to disease predisposition among patients with gender-dependent conditions. Since idiopathic PAH (IPAH) is more prevalent in women, we hypothesized that the 2D:4D ratio could predict a female’s predisposition to developing PAH, reflecting an interaction between ET-1 and sex hormones.

Method: This study analyzed 13 female patients with IPAH at Keio University Hospital and 41 unrelated agematched controls. The right hand of patients and controls was photographed using a digital camera and two experienced scorers measured finger lengths and 2D:4D ratios.

Key findings: The IPAH and control groups had a mean age of 43.2 ± 3.5 and 40.9 ± 1.7 years, respectively. The 2D:4D digit ratio was significantly higher for patients with IPAH than for the control women; 0.975 ± 0.041 vs. 0.940 ± 0.038, P<0.05. The age at onset of PAH did not correlate with the ratio.

Significance: Female patients with IPAH in this study had a higher 2D:4D digit ratio than age-matched healthy controls, suggesting lower prenatal circulating testosterone levels. In conclusion, the 2D:4D digit ratio is a useful biomarker for IPAH, and prenatal testosterone level could be an important factor for the protection against developing IPAH.