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

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.

Digit ratio (2D:4D) is not related to cardiovascular diseases or their risk factors in menopausal women

“…The lack of significant associations in this study might indicate that 2D:4D is not a useful proxy for CVDs in women. This is in contrast to recent studies on 2D:4D and different cardiovascular‐related outcomes, including their causality of death (Asuku et al, 2019; Lenz & Kornhuber, 2018;Wang et al, 2018; Yamamoto et al, 2015). However, our study had one of the largest sample sizes up to date, and included a group of relatively homogenous women of white, European descent.…”

“…Negative correlation was observed between 2D:4D and adiponectin and HDL‐cholesterol, which is also relevant to CVD risk. A study among Japanese women have found a significantly higher 2D:4D in a group with idiopathic pulmonary hypertension compared to a control group (Yamamoto et al, 2015). A more recent cross‐national study on sex‐specific relation between 2D:4D and causes of mortality in 23 countries revealed that among women, 2D:4D is related to ischaemic heart disease as a cause of death (normalized to the national means) (Lenz & Kornhuber, 2018).…”

“…A more recent cross‐national study on sex‐specific relation between 2D:4D and causes of mortality in 23 countries revealed that among women, 2D:4D is related to ischaemic heart disease as a cause of death (normalized to the national means) (Lenz & Kornhuber, 2018). However, previous studies (Asuku et al, 2019; Wang et al, 2018; Yamamoto et al, 2015) were mostly based on small sample sizes, and some of them were conducted among specific ethnic populations.…”

The relationship between second-to-fourth digit ratio (2D:4D), muscle strength and body composition to bone mineral density in young women

“…So, during that period, if there are changes in the environment of the uterus (such as malnutrition or changes in the level of hormone within the uterus), not only will systems and organs structure of the fetus change, but also it affects ratio of fingers. Therefore, studying the ratio of fingers can indirectly indicate development of embryo during the fetal period in the uterus and the changes occurring in this period (Lu, et al, 2015;Yamamoto, Tamura, Ono, Takei, & Sano, 2015).…”

The association between second to fourth digit ratio, reproductive and general health among women: findings from an Israeli pregnancy cohort

“…Several studies found 2D:4D to be associated with reproductive cancers 25,30,31 . As for general health characteristics, 2D:4D was associated with various cancers 32,33 , idiopathic pulmonary hypertension 34 and other morbidities such as systemic lupus erythematosus 35 , autism spectrum disorders 36 , and congenital adrenal hyperplasia 37,38 .…”