Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study

Zahra Salehi; Mohammad Mehdi Naghizadeh; Sajjad Ghane Ezabadi; Azadeh Ebrahimitirtashi; Naghmeh Abbasi Kasbi; Faezeh Khodaie; Shahram Aliyari; Fereshteh Ashtari; Seyed Mohammad Baghbanian; Seyed Massood Nabavi; Samaneh Hosseini; Nazanin Razazian; Vahid Shaygannejad; Nastaran Majdi-Nasab; Mohammad Hossein Harirchian; Asghar Bayati; Hoda Kamali; Nahid Hosseni Nejad Mir; Nahid Beladi Moghadam; Maryam Poursadeghfard; Hossein Mozhdehipanah; Nazanin Jalali; Mohammad Ali Nahayati; Fardin Faraji; Naser Kamyari; Mohammad Ali Sahraian; Zhila Maghbooli; Sharareh Eskandarieh

doi:10.1016/j.heliyon.2024.e32946

Consanguineous marriage among familial multiple sclerosis subjects: A national registry-based study

Heliyon. 2024 Jun 15;10(12):e32946. doi: 10.1016/j.heliyon.2024.e32946. eCollection 2024 Jun 30.

Authors

Zahra Salehi^{1

2}, Mohammad Mehdi Naghizadeh³, Sajjad Ghane Ezabadi⁴, Azadeh Ebrahimitirtashi⁴, Naghmeh Abbasi Kasbi⁴, Faezeh Khodaie⁴, Shahram Aliyari⁵, Fereshteh Ashtari⁶, Seyed Mohammad Baghbanian⁷, Seyed Massood Nabavi⁸, Samaneh Hosseini⁹, Nazanin Razazian¹⁰, Vahid Shaygannejad⁶, Nastaran Majdi-Nasab¹¹, Mohammad Hossein Harirchian¹², Asghar Bayati¹³, Hoda Kamali¹⁴, Nahid Hosseni Nejad Mir¹⁵, Nahid Beladi Moghadam¹⁶, Maryam Poursadeghfard¹⁷, Hossein Mozhdehipanah¹⁸, Nazanin Jalali¹⁹, Mohammad Ali Nahayati²⁰, Fardin Faraji²¹, Naser Kamyari²², Mohammad Ali Sahraian⁴, Zhila Maghbooli⁴, Sharareh Eskandarieh⁴

Affiliations

¹ Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran.
² Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.
³ Noncommunicable Diseases Research Center, Fasa University of Medical Sciences, Fasa, Iran.
⁴ Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
⁵ Division of Applied Bioinformatics, German Cancer Research Center DKFZ Heidelberg, Heidelberg, Germany.
⁶ Isfahan Neurosciences Research Center, Isfahan University of Medical Sciences, Isfahan, Iran.
⁷ Department of Neurology, Booalicina Hospital, Mazandaran University of Medical Sciences, Sari, Iran.
⁸ Department of Regenerative Medicine, Royan Institute for Stem Cell Technology and Biology, Tehran, Iran.
⁹ Neurosciences Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
¹⁰ Department of Neurology, School of Medicine, Imam Reza Hospital, Kermanshah University of Medical Sciences, Iran.
¹¹ Musculoskeletal Rehabilitation Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
¹² Department of Neurology, School of Medicine, Iranian Center of Neurological Research, Neuroscience Institute, Imam Khomeini Hospital, Tehran University of Medical Sciences, Iran.
¹³ Department of Neurology, Shahrekord University of Medical Sciences and Health Services, Shahrekord, Iran.
¹⁴ Neurology Research Center, Kerman University of Medical Sciences, Kerman, Iran.
¹⁵ Department of Internal Medicine, School of Medicine, Shohadaye Ashayer Hospital, Lorestan University of Medical Sciences, Khorramabad, Iran.
¹⁶ Department of Neurology, School of Medicine, Imam Hossein Hospital, Shahid Beheshti University of Medical Sciences, Iran.
¹⁷ Clinical Neurology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
¹⁸ Department of Neurology, Qazvin University of Medical Sciences, Qazvin, Iran.
¹⁹ Department of Neurology, School of Medicine, Rafsanjan University of Medical Sciences, Rafsanjan, Iran.
²⁰ Department of Neurology, Ghaem Hospital, Mashhad University of Medical Sciences, Mashhad, Iran.
²¹ Department of Neurology, School of Medicine, Arak University of Medical Sciences, Arak, Iran.
²² Department of Biostatistics and Epidemiology, School of Health, Abadan University of Medical Sciences, Abadan, Iran.

Abstract

Background: The rising prevalence of familial multiple sclerosis (MS) in Iran has spurred interest in the potential impact of parental consanguinity on the risk of developing the disease. This study aims to aggregate current knowledge on parental consanguinity and its possible effect on MS risk, particularly among familial MS patients from various regions and ethnicities in Iran. The objective is to enhance the understanding of MS genetics and encourage further research in this field.

Materials and methods: A cross-sectional study was conducted on clinically definite familial MS (FMS) patients registered in the nationwide MS registry of Iran (NMSRI). Data were extracted and supplemented with structured telephone follow-ups to gather detailed histories of MS in relatives and the familial relationships of the patients' parents. A family penetration score was proposed. Descriptive statistics and inferential statistical tests were used to analyze the data at a significance level of 0.05, adhering to ethical guidelines.

Results: Out of 19,911 individuals registered in the NMSRI, 2307 FMS patients across 13 provinces were included in the final analysis. Among these, 385 (19.3 %) reported parental consanguinity, with 283 (14.2 %) having parents who were cousins and 102 (5.1 %) having parents who were distant relatives. The data showed no significant association between parental kinship and variables such as MS phenotype, number of affected relatives with MS, hospitalization rates, and expanded disability status scale score. Similarly, MS severity did not differ based on parental consanguinity (P-value >0.05). While the rate of consanguineous marriage was higher among patients with an onset age less than 18 years, there was no statistically significant difference in disease onset age based on parental consanguinity status.

Conclusion: Our study highlights the complexity of factors influencing MS development, including genetic and environmental components. These results highlight the need for further research to achieve a more comprehensive understanding of MS etiology.

Keywords: Familial multiple sclerosis; Iran; Multiple sclerosis; Parental consanguinity.