Association between Body Mass Index and Medication-Overuse Headache among Individuals with Migraine: A Cross-Sectional Study.

INTRODUCTION: Medication-overuse headache (MOH) is a secondary chronic headache disorder that occurs in individuals with a pre-existing primary headache disorder, particularly migraine disorder. Obesity is often combined with chronic daily headaches and is considered a risk factor for the transformation of episodic headaches into chronic headaches. However, the association between obesity and MOH among individuals with migraine has rarely been studied. The present study explored the association between body mass index (BMI) and MOH in people living with migraine. METHODS: This cross-sectional study is a secondary analysis of data from the Survey of Fibromyalgia Comorbidity with Headache study. Migraine and MOH were diagnosed using the criteria of the International Classification of Headache Disorders, 3rd Edition. BMI (kg/m2) is calculated by dividing the weight (kg) by the square of the height (m). Multivariable logistic regression analysis was used to evaluate the association between BMI and MOH. RESULTS: A total of 2,251 individuals with migraine were included, of whom 8.7% (195/2,251) had a concomitant MOH. Multivariable logistic regression analysis, adjusted for age, sex, education level, headache duration, pain intensity, headache family history, chronic migraine, depression, anxiety, insomnia, and fibromyalgia, demonstrated there was an association between BMI (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.11; p = 0.031) and MOH. The results remained when the BMI was transformed into a category. Compared to individuals with Q2 (18.5 kg/m2 ≤ BMI ≤23.9 kg/m2), those with Q4 (BMI ≥28 kg/m2) had an adjusted OR for MOH of 1.81 (95% CI, 1.04-3.17; p = 0.037). In the subgroup analyses, BMI was associated with MOH among aged more than 50 years (OR, 1.13; 95%, 1.03-1.24), less than high school (OR, 1.08; 95%, 1.01-1.15), without depression (OR, 1.06; 95%, 1.01-1.12), and without anxiety (OR, 1.06; 95%, 1.01-1.12). An association between BMI and MOH was found in a sensitivity analysis that BMI was classified into four categories according to the World Health Organization guidelines. CONCLUSION: In this cross-sectional study, BMI was associated with MOH in Chinese individuals with migraine.

Associations of type 2 diabetes and the risk of migraine in Chinese populations.

AIM: We aimed to explore the relationship between type 2 diabetes mellitus (T2DM) and the incidence rate of migraine in a Chinese population, and analyze the clinical characteristics of migraine patients with T2DM. METHODS: Data on the study cohort of 9873 individuals were obtained from the China Health and Retirement Longitudinal Study (CHARLS). The incidence rate of migraine from 2015 to 2018 was assessed. The Cox proportional hazards model was used to estimate hazard ratios (HRs) and their 95% confidence intervals (CIs) for the relationship between T2DM and the incidence of migraine. In addition, a cross-sectional study including 168 migraine patients was conducted in Xiamen, China. Migraine patients were grouped according to their T2DM status. Multivariable linear regression models were used to estimate ßs and their 95% CIs for the relationship between migraine characteristics and T2DM. RESULTS: The cumulative incidence rate of migraine from 2015 to 2018 in the T2DM group and control group was 7.26% [6.04%.8.65%] and 8.91% [8.27%.9.58%], respectively. The risk of migraine in patients with T2DM was reduced by 21% (HR 0.79 [0.65;0.95]) compared to patients with no T2DM after adjustment for confounders. The cross-sectional study showed that the presence of T2DM significantly reduced migraine frequency and relieved migraine intensity. CONCLUSION: This was the first study to validate that T2DM reduced the risk of migraine in a Chinese population cohort. Patients with migraine and T2DM may experience significant relief from their headache symptoms. Carrying out relevant mechanistic research may help to identify new targets for migraine treatment and contribute to further understanding the impact of T2DM or related metabolic disorders on an individual's health.

Serum neurofilament light chain levels in migraine patients: a monocentric case-control study in China.

PURPOSE: Serum neurofilament light chain (sNfL) can reflect nerve damage. Whether migraine can cause neurological damage remain unclear. This study assesses sNfL levels in migraine patients and explores whether there is nerve damage in migraine. METHODS: A case-control study was conducted in Xiamen, China. A total of 138 migraine patients and 70 healthy controls were recruited. sNfL (pg/mL) was measured on the single-molecule array platform. Univariate, Pearson correlation and linear regression analysis were used to assess the relationship between migraine and sNfL levels, with further subgroup analysis by migraine characteristics. RESULTS: Overall, 85.10% of the 208 subjects were female, with a median age of 36 years. sNfL levels were higher in the migraine group than in the control group (4.85 (3.49, 6.62) vs. 4.11 (3.22, 5.59)), but the difference was not significant (P = 0.133). The two groups showed an almost consistent trend in which sNfL levels increased significantly with age. Subgroup analysis showed a significant increase in sNfL levels in patients with a migraine course ≥ 10 years (ß = 0.693 (0.168, 1.220), P = 0.010). Regression analysis results show that age and migraine course are independent risk factors for elevated sNfL levels, and there is an interaction between the two factors. Patients aged < 45 years and with a migraine course ≥ 10 years have significantly increased sNfL levels. CONCLUSIONS: This is the first study to evaluate sNfL levels in migraine patients. The sNfL levels significantly increased in patients with a migraine course ≥ 10 years. More attention to nerve damage in young patients with a long course of migraine is required.

Status of diagnosis and preventative treatment for primary headache disorders: real-world data of unmet needs in China.

BACKGROUND: Headache disorders are widely prevalent and pose a considerable economic burden on individuals and society. Globally, misdiagnosis and inadequate treatment of primary headache disorders remain significant challenges, impeding the effective management of such conditions. Despite advancements in headache management over the last decade, a need for comprehensive evaluations of the status of primary headache disorders in China regarding diagnosis and preventative treatments persists. METHODS: In the present study, we analyzed the established queries in the Survey of Fibromyalgia Comorbidity with Headache (SEARCH), focusing on previous diagnoses and preventative treatment regimens for primary headache disorders. This cross-sectional study encompassed adults diagnosed with primary headache disorders who sought treatment at 23 hospitals across China between September 2020 to May 2021. RESULTS: The study comprised 2,868 participants who were systematically examined. Migraine and tension-type headaches (TTH) constituted a majority of the primary headache disorders, accounting for 74.1% (2,124/2,868) and 23.3% (668/2,868) of the participants, respectively. Medication overuse headache (MOH) affected 8.1% (231/2,868) of individuals with primary headache disorders. Over half of the individuals with primary headache disorders (56.6%, 1,624/2,868) remained undiagnosed. The previously correct diagnosis rates for migraine, TTH, TACs, and MOH were 27.3% (580/2,124), 8.1% (54/668), 23.2% (13/56), and 3.5% (8/231), respectively. The misdiagnosis of "Nervous headache" was found to be the most prevalent among individuals with migraine (9.9%, 211/2,124), TTH (10.0%, 67/668), trigeminal autonomic cephalalgias (TACs) (17.9%, 10/56), and other primary headache disorders (10.0%, 2/20) respectively. Only a minor proportion of individuals with migraine (16.5%, 77/468) and TTH (4.7%, 2/43) had received preventive medication before participating in the study. CONCLUSIONS: While there has been progress made in the rate of correct diagnosis of primary headache disorders in China compared to a decade ago, the prevalence of misdiagnosis and inadequate treatment of primary headaches remains a veritable issue. As such, focused efforts are essential to augment the diagnosis and preventive treatment measures related to primary headache disorders in the future.

The prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache: The survey of fibromyalgia comorbid with headache.

OBJECTIVE: The aims were to explore the prevalence and clinical features of fibromyalgia in Chinese hospital patients with primary headache. BACKGROUND: Studies done in non-Chinese populations suggest that around one-third of patients with primary headache have fibromyalgia, but data from mainland China are limited. Investigations into the prevalence and clinical features of fibromyalgia in Chinese patients with primary headache would improve our understanding of these two complex disease areas and help guide future clinical practice. METHODS: This cross-sectional study included adults with primary headache treated at 23 Chinese hospitals from September 2020 to May 2021. Fibromyalgia was diagnosed using the modified 2010 American College of Rheumatology criteria. Mood and insomnia were evaluated employing the Hospital Anxiety and Depression Scale and the Insomnia Severity Index. RESULTS: A total of 2782 participants were analyzed. The fibromyalgia prevalence was 6.0% (166/2782; 95% confidence interval: 5.1%, 6.8%). Compared to primary headache patients without combined fibromyalgia, patients with primary headache combined with fibromyalgia were more likely to be older (47.8 vs. 41.7 years), women (83.7% [139/166] vs. 72.8% [1904/2616]), less educated (65.1% [108/166] vs. 45.2% [1183/2616]), and with longer-duration headache (10.0 vs. 8.0 years). Such patients were more likely to exhibit comorbid depression (34.3% [57/166] vs. 9.9% [260/2616]), anxiety (16.3% [27/166] vs. 2.7% [70/2612]), and insomnia (58.4% [97/166] vs. 17.1% [447/2616]). Fibromyalgia was more prevalent in those with chronic (rather than episodic) migraine (11.1% [46/414] vs. 4.4% [72/1653], p < 0.001) and chronic (rather than episodic) tension-type headache (11.5% [27/235] vs. 4.6% [19/409], p = 0.001). Most fibromyalgia pain was in the shoulders, neck, and upper back. CONCLUSIONS: The prevalence of fibromyalgia in mainland Chinese patients with primary headache was 6.0%. Fibromyalgia was more common in those with chronic rather than episodic headache. The most common sites of fibromyalgia pain were the neck, shoulders, and back.

Involvement of the Tetraspanin 2 (TSPAN2) Gene in Migraine: A Case-Control Study in Han Chinese.

Tetraspanin 2 (TSPAN2) belongs to the tetraspanin superfamily. Previous studies have identified significant associations of the TSPAN2 single nucleotide polymorphisms (SNPs) rs12134493 and rs2078371 with migraine in Western populations; however, these associations need to be confirmed in the Chinese Han population. In addition, we carried out further studies to see whether TSPAN2 is associated with susceptibility to migraine to provide new clinical evidence. A case-control study (425 patients with migraine and 425 healthy controls) in a Chinese Han population was performed to evaluate the associations between migraine and TSPAN2 via a genotype-phenotype analysis between TSPAN2 and clinical symptoms. The SNP rs2078371 was found to be significantly associated with migraines especially in migraines without aura (MO) and in female patients. Meta-analysis revealed that the A allele of rs12134493 was significantly associated with migraines (OR = 1.14, P = 0.0001). Our findings suggested that TSPAN2 is a potential susceptibility factor for migraines. To confirm our results, a large-scale Chinese Han population study should be conducted. Considering that these two SNPs have not been definitively shown to affect TSPAN2 or to regulate nearby genes in this genomic region, the biological function and molecular mechanism of TSPAN2 in migraine should be further explored.

New evidence for involvement of ESR1 gene in susceptibility to Chinese migraine.

Migraine is a common and disabling nervous system disease with a significant genetic predisposition. The sex hormones play an important role in the pathogenesis of migraine. However, the conclusions of the previous genetic relation studies are conflicting. The aim of this study is to determine whether variants in genes involved in estrogen receptor and estrogen hormone metabolism are related to Chinese migraine. By employing a case-control approach, 8 SNPs in the ESR1, ESR2, and CYP19A1 genes are studied in a cohort of 494 migraine cases and 533 controls. In addition, genotyping is performed using Sequenom MALDI-TOF mass spectrometry iPLEX platform. Univariate and multivariate analyses are carried out by logistic regression. The corresponding haplotypes are studied with the Haploview software and gene-gene interaction is assessed using the Generalized Multifactor Dimensionality Reduction (GMDR) analysis. There are significant differences in allelic distributions for rs2234693 and rs9340799 in ESR1 gene between patients with migraine and control subjects. Univariate logistic analysis shows that rs2234693 and rs9340799 are risk factors for migraine, but multivariate analysis reveals that only rs2234693 is significant associated with migraine. In the subgroup analysis, rs2234693 in ESR1 gene is found associated with menstrually related migraine. Further haplotypic analysis shows that rs2234693-rs9340799 TA haplotype serves as risk haplotype for migraine. The GMDR analysis identifies rs2234693 in ESR1 alone to be a crucial candidate in migraine susceptibility. This study is in agreement with the previous studies that variants in the ESR1 gene are associated with migraine suggesting that it plays a role in the migraine process.

Analysis of LRRK2, SNCA, and ITGA8 Gene Variants with Sporadic Parkinson's Disease Susceptibility in Chinese Han Population.

Background. Parkinson's disease (PD) is an age-related neurodegenerative disease affected by multiple genetic and environmental factors. We performed a case-control study on candidate gene to scrutinize whether genetic variants in LRRK2, SNCA, and ITGA8 genes could be associated with sporadic PD in Chinese Han population. Methods. Five single-nucleotide polymorphisms (SNPs) of LRRK2 (rs1491942), SNCA (rs2301134, rs2301135, and rs356221), and ITGA8 (rs7077361) were selected and genotyped among 583 unrelated PD patients and 558 healthy controls. Results. Rs1491942 of LRRK2 gene had a significantly higher genotype frequency (P = 3.543E - 09) and allelic G/C frequencies (P = 2.601E - 10) in PD patients than controls. Rs2301135 of SNCA gene also showed an obvious difference in genotype frequency (P = 4.394E - 07) and allelic G/C frequencies (P = 9.116E - 13) between PD patients and controls. SNPs rs2301134 and rs356221 of SNCA gene and rs7077361 of ITGA8 gene lacked the significant association with the susceptibility of PD in Chinese Han population. Conclusions. Our study firstly expresses that rs1491942 of LRRK2 and rs2301135 of SNCA gene are substantially associated with sporadic Parkinson's disease in Chinese Han population.

Association study of TREM2 polymorphism rs75932628 with leucoaraiosis or Parkinson's disease in the Han Chinese population.

OBJECTIVES: The previously reported functional mutation rs75932628-T (p.R47H) in the triggering receptor expressed on myeloid cells 2 (TREM2) is a genetic risk factor for Alzheimer's disease, Parkinson's disease (PD) and frontotemporal dementia, in European populations. This study aims to assess the genetic association of the variant rs75932628-T with PD and leucoaraiosis (LA) in a Han Chinese population. SETTING: This population-based study was conducted in China by Xiamen University and its affiliated hospital. PARTICIPANTS: 308 patients with LA, 342 patients with PD and 198 healthy blood donors were recruited from the First Affiliated Hospital of Xiamen University. OUTCOME MEASURES: Genotyping was performed by molecular beacon real-time PCR and Sanger sequencing. RESULTS: None of our participants carried the rs75932628-T mutation. CONCLUSIONS: Our results corroborate and extend previous findings, concluding that the variant rs75932628-T (p.R47H) in TREM2 is not a risk factor for LA or PD in the Han Chinese population.

Case-control study of GRIA1 and GRIA3 gene variants in migraine.

BACKGROUND: As the most abundant excitatory neurotransmitter in the central nervous system, glutamate has been accepted to play a major role in the pathophysiology of migraine. The previous studies have reported the glutamate receptor ionotropic GRIA1 and GRIA3 genes variants associated with migraine. The project aims to investigate the polymorphisms in both genes for their association with migraine in the Chinese Han population. METHODS: A Han-Chinese case-control population, including 331 unrelated female migraine patients and 330 matched controls, was studied. Variants in genes (GRIA1 and GRIA3) were genotyped by Multiplex SNaPshot assay. RESULTS: In the group of patients, the frequency of allele C was 84.1 % (557 C alleles) and allele T was 15.9 % (105 T alleles) for the GRIA1 (rs2195450) in migraineurs, this was significantly as compared with the controls (P = .001, OR = 1.786, 95 % CI: 1.28-2.49). And an association was also seen in the migraine with aura (MA) subtype (P = .012, OR = 2.092, 95 % CI: 1.17-3.76) and migraine without aura (MO) subtype (P = .002, OR = 1.737, 95 % CI: 1.23-2.45). However, no evidence was found that GRIA1 (rs548294) or GRIA3 (rs3761555) is associated with migraine. CONCLUSION: Our data of this study confirmed the association of GRIA1 (rs2195450) to female migraine (MA, MO) susceptibility in the Chinese Han population. The result provides evidence that the glutamatergic system is implicated in the pathophysiology of migraine.

PRDM16 rs2651899 variant is a risk factor for Chinese common migraine patients.

OBJECTIVE: Recent genome-wide association studies (GWAS) have identified 3 loci in or near PRDM16 (1p36.32, rs2651899), LRP1 (12q13.3, rs11172113) and TRPM8 (2q37.1, rs10166942) in the population-based Women's Genome Health Study (WGHS) of migraine, and 2 loci in or near TRPM8 and LRP1 were repeated in European GWAS study. To evaluate whether the same variants are related to migraine in Chinese population, we investigated migraine with aura (MA) and migraine without aura (MO) patients of Chinese Han ethnicity in mainland China. METHODS: A case-control study in a cohort of 207 migraine cases and 205 ethnically matched controls was conducted by using the dual-color fluorescence resonance energy transfer (FRET) probes analysis. RESULTS: The genotypes of all polymorphisms in 2 groups followed the Hardy-Weinberg equilibrium. We found significant differences in allele distribution of rs2651899 variant in PRDM16 between MO patients and control subjects (P = .049, OR = 1.335, 95%CI 1.001-1.782), and there were no difference between MA patients and controls in the frequency of genotype and allele. Also, no significant differences in genotypic and allelic distributions between MA or MO patients and controls were observed in the polymorphisms of rs10166942 of TRPM8 and rs11172113 of LRP1, and there was no significant difference comparing male with female in all loci. CONCLUSION: Our data suggested that rs2651899 variant in PRDM16 plays a potential role in Chinese MO migraine susceptibility, and gender may not play a role.

Association of MTHFR C677T polymorphism with susceptibility to migraine in the Chinese population.

A number of genes have been implicated in the pathogenesis of migraine, a common neurological disorder also in China. However, data on association of genetic variations with migraine susceptibility among Chinese, which might be different from people of other ethnic background, are still scarce. We have therefore investigated the association of polymorphisms in four genes, MTHFR C677T, ACE I/D, MAOA T941G and TNF-ß G252A, which are considered to be with risk of migraine. A case-control study including a cohort of 151 migraine cases and 137 ethnically matched controls was conducted. The genotypes of each polymorphism followed the Hardy-Weinberg equilibrium in the two groups. Genotypic distribution of MTHFR C677T was significantly different with higher frequency of allele T in the migraine cohort as compared with that in controls (OR=1.686, 95%CI: 1.175-2.420, P=0.004). No difference was found between migraine with aura (MA) patients and controls, but T allele frequency was significantly higher in migraine without aura (MO) than in controls (OR=1.744, 95% CI: 1.202-2.532, P=0.003). No difference in genotypic and allelic distributions was observed between migraine patients and controls for the other polymorphisms, including ACE I/D, MAOA T941G, and TNF-ß G252A. Our data suggested that MTHFR C677T polymorphism plays a role in Chinese migraine susceptibility, especially in MO.

P268S in NOD2 associates with susceptibility to Parkinson's disease in Chinese population.

BACKGROUND: The cause of almost all cases of Parkinson's disease (PD) remains unknown. Recent years have seen an explosion in the rate of discovery of genetic defects linked to PD. Different racial and geographical populations may have different distributions of genetic variants. METHODS: In the current study, we screened the following genetic variants, including some rare mutations and single nucleotide polymorphisms (SNPs), in a pedigree and cases-controls. To best of our knowledge, we first screened these variants known to be associated with neurodegeneration disease, E46K (rs104893875) in SNCA, A1442P in LRRK2, IVS9 in PARK2, A350V in SLC41A1, P268S (rs2066842), R702W (rs2066844), G908R (rs2066845), 1007fs (rs2066847) in NOD2 and G2385R (rs34778348) in LRRK2 from southern China population. Genotyping was performed by jointly using primers overlapping polymerase chain reaction (PCR) site-directed mutagenesis, restriction fragment length polymorphism (RFLP), and capillary electrophoresis (CE). RESULTS: We didn't discover above 9 variants in the family members of the pedigree. Furthermore, of 237 patients with sporadic Parkinson's disease and 190 controls, no heterozygosity or homozygosity were found from E46K, A1442P, A350V, R702W, G908R, or 1007fs but heterozygosity onto G2385R, IVS9, and P268S. No significant difference between cases and controls was found in both allele frequency (P = 0.572) and genotype frequency (P = 0.348) of IVS9. However, significant differences in genotype frequency (P = 0.009) of G2385R were consistent with prior observation. Eight patients with Parkinson's disease (2 women and 6 men are over the age of 50 years at onset of PD) carried the P268S heterozygous variation in NOD2. There was no heterozygosity or homozygosity of P268S in the controls. Genotype frequency of P268S (P = 0.0450) had significant differences. CONCLUSIONS: Our results suggested that the P268S variant in NOD2 might be a risk factor for susceptibility to sporadic Parkinson's disease in Chinese populations. It also implied that the inflammatory response may play a role in PD.

LRRK2 R1628P variant is a risk factor of Parkinson's disease among Han-Chinese from mainland China.

Mutations in LRRK2, the gene that encodes leucine-rich repeat kinase 2 (LRRK2), are associated with autosomal dominant and sporadic forms of Parkinson's disease (PD) and are the most common genetic causes of PD. Recently, a R1628P variant has been reported as a risk factor for PD in Taiwan and Singapore. To determine the association of this variant and PD in the Han-Chinese population from mainland China, we analyzed its frequency in a cohort of 600 patients and 459 unrelated healthy controls. Forty (6.7%) patients were heterozygous and 3 (0.5%) homozygous for the R1628P variant, which was significantly more frequent than in the controls [2.4% heterozygous and 0.0% homozygous, Odds ratio = 3.14, 95%CI: 1.60-6.17, P < 0.01]. Considering the age at onset, this difference was found only in late-onset PD (older than 50) [Odds ratio = 3.76, 95% CI: 1.90-7.45, P < 0.01]. Our data confirms that the LRRK2 R1628P variant is associated with an increased risk to develop late onset PD in the ethnic Han-Chinese population.