Abstract
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.
Highlights
Various digit ratios, and in particular the second to fourth digit ratio, are sexually dimorphic characteristics in humans [1], and evidence accumulated over the past decade indicates that the 2D:4D ratio is determined by prenatal estrogen and testosterone concentrations [2].Some studies have already investigated the links between 2D:4D ratio and the etiology of sex-dependent behaviours with respect to immune system disorders, cardiovascular diseases like myocardial infarction [3], some cancers [4], and a number of adult-onset diseases prevalent among men such as amyotrophic lateral sclerosis (ALS) [5]
The idiopathic pulmonary arterial hypertension (IPAH) patient group had significantly higher 2D:4D ratios compared to the healthy control group
The present study revealed that female patients with IPAH had a higher 2D:4D ratio than control women, suggesting that low serum testosterone prenatal levels and high estrogen prenatal levels in the uterus could predispose females to developing pulmonary arterial hypertension (PAH)
Summary
Some studies have already investigated the links between 2D:4D ratio and the etiology of sex-dependent behaviours with respect to immune system disorders, cardiovascular diseases like myocardial infarction [3], some cancers [4], and a number of adult-onset diseases prevalent among men such as amyotrophic lateral sclerosis (ALS) [5]. The 2D:4D ratio is a potential predictor of fertility, and sex-dependent disease. This study sought to investigate whether digit ratios have clinical importance as a marker of sexual predisposition to PAH. Since patients with PAH are predominantly women, we hypothesized a link between 2D:4D ratio and disease predisposition in IPAH, reflecting the association between sex steroids and ET-1
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