The Impact of Parental Consanguinity and Familial Aggregation on Multiple Sclerosis Risk: Insights from an Iranian

Multiple sclerosis (MS) is a chronic autoimmune disorder of the central nervous system characterized by the destruction of myelin sheaths, leading to disrupted nerve signal transmission and significant morbidity. The prevalence of MS in Iran is 29.3 cases per 100,000 individuals, with an incidence of 3.4 cases per 100,000 individuals. This case-control study, conducted by Saeed Vaheb and colleagues, investigates the role of parental consanguinity (PC) and familial multiple sclerosis (FMS) in the risk of developing MS among people with MS (pwMS) in Isfahan, Iran.

The study was conducted from September 2022 to September 2023 at the MS clinic of Kashani Hospital, Isfahan, Iran. It included 4264 pwMS and 400 healthy controls (HC). Data on demographic and clinical characteristics, as well as history of PC and FMS, were collected. The relationships between PC, FMS, and developing MS were assessed using multinomial logistic regression analysis, with odds ratios (OR) and 95% confidence intervals (CI) computed.

The prevalence of PC and FMS among pwMS was 29.3% and 24%, respectively. The study found significant associations between a history of PC (OR = 3.03, 95% CI: 2.23 to 4.13, p < 0.001) and FMS (OR = 5.42, 95% CI: 3.51 to 8.38, p < 0.001) with the odds of developing MS. The analysis also revealed that PC increased the likelihood of developing various MS phenotypes: relapsing-remitting MS (RRMS) (OR = 2.5, p < 0.001), secondary progressive MS (SPMS) (OR = 3.5, p < 0.001), and primary progressive MS (PPMS) (OR = 4.3, p < 0.001). Similarly, FMS was associated with increased odds of developing these MS phenotypes: RRMS (OR = 5.57, p < 0.001), SPMS (OR = 6.01, p < 0.001), and PPMS (OR = 4.04, p < 0.001).

The study highlights the significant influence of genetic factors in the development of MS. The findings indicate that both PC and FMS are substantial risk factors for developing MS. The study found a slightly lower prevalence of PC among pwMS compared to previous studies, while the prevalence of FMS was consistent with regional data.

The practice of consanguinity, which is common in Middle Eastern nations, particularly Iran, appears to play a significant role in the genetic predisposition to MS. The study suggests that consanguinity may increase the genetic load of MS, leading to higher susceptibility among offspring.

The study acknowledges limitations, including selection and recall bias, and the lack of genome sequencing to validate findings. The retrospective nature of chart reviews also limits the ability to accurately identify case and control groups and test clinical variables.

Conclusion
The study concludes that a history of PC and FMS significantly increases the risk of developing MS. The findings underscore the importance of considering genetic factors, including consanguinity and familial aggregation, in understanding MS risk. Further research with genome sequencing and larger populations is recommended to validate these findings and explore the underlying genetic mechanisms.

References:
Vaheb, S., Panah, M. Y., Afshari-Safavi, A., Ghaffary, E. M., Shaygannejad, A., Shaygannejad, V., & Mirmosayyeb, O. (2024). The Role of Parental Consanguinity and Familial Aggregation in Development of Multiple Sclerosis: A Case-control Study.